The efficacy of anal fistula plug in fistula‐in‐ano: a systematic review

Aims To assess the efficacy of anal fistula plug (AFP) procedure for the treatment of fistula‐in‐ano especially the complex fistulas. Method The database of PUBMED, MEDLINE, SCOPUS, EMBASE and COCHRANE LIBRARY for the period 1995–2009 was searched. A systematic analysis was carried to evaluate the success rate of AFP procedure in fistula‐in‐ano. Results A total of 25 studies were extracted and 12 (n = 317) were finally included in the systematic review. The follow‐up period ranged from 3.5 to 12 months. The AFP procedure had a success rate (patient cure rate) ranging from 24% to 92%. In complex fistula‐in‐ano in prospective studies (8/12 studies), the success rate was 35–87%. The success rate in patients with Crohn’s disease was 29–86%. The success rate in the patients with single tracts was 44–93% and in patients with multiple tracts, success ranged from 20% to 71%. The abscess formation/sepsis rate was 4–29% (11/108) and the plug extrusion rate was 4–41% (42/232–19%). Conclusion Anal fistula plug procedure has a success rate ranging from 24% to 92% in different studies. In prospective studies of complex fistula‐in‐ano, there was a moderate success rate of 35–87%. As AFP is associated with low morbidity and sepsis, it appears to be a safe procedure. Further randomized controlled trials studying objective parameters of fistula healing are needed to substantiate these findings.     

Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates

An important question in memory development is understanding the differences between effector CD8 T cells that die versus effector cells that survive and give rise to memory cells. In this study, we provide a comprehensive phenotypic, functional, and genomic profiling of terminal effectors and memory precursors. Using killer cell lectin-like receptor G1 as a marker to distinguish these effector subsets, we found that despite their diverse cell fates, both subsets possessed remarkably similar gene expression profiles and functioned as equally potent killer cells. However, only the memory precursors were capable of making interleukin (IL) 2, thus defining a novel effector cell that was cytotoxic, expressed granzyme B, and produced inflammatory cytokines in addition to IL-2. This effector population then differentiated into long-lived protective memory T cells capable of self-renewal and rapid recall responses. Experiments to understand the signals that regulate the generation of terminal effectors versus memory precursors showed that cells that continued to receive antigenic stimulation during the later stages of infection were more likely to become terminal effectors. Importantly, curtailing antigenic stimulation toward the tail end of the acute infection enhanced the generation of memory cells. These studies support the decreasing potential model of memory differentiation and show that the duration of antigenic stimulation is a critical regulator of memory formation.     

Synthesis and cytotoxic evaluation of substituted 3-(3′-indolyl-/3′-pyridyl)-isoxazolidines and bis-indoles

Regio- and stereoselective 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (10) were carried out with different mono-substituted, disubstituted and cyclic dipolarophiles under mono-mode microwave irradiation to obtain substituted 3-(indol-3′-yl)-N-phenyl-isoxazolidines (16–22). Reactions of nitrone (10) with allenic esters under similar conditions afforded, via a domino process, bis-indole derivatives (23a–c) along with compounds 24 and 25. Similarly, reactions of C-(3-pyridyl)-N-phenylnitrone (26) with mono-substituted, disubstituted and cyclic dipolarophiles were carried out in refluxing dry toluene to obtain substituted 3-(3′-pyridyl)-N-phenylisoxazolidines (27–34). Some of the compounds (16f, 18b, 23a, 23c, 27c and 29f) display significant cytotoxicity against a number of human cancer cell lines.     

Hematopoietic Stem Cell Homing to Injured Tissues

The use of stem cells is considered a promising therapy for tissue regeneration and repair, particularly for tissues injured through degeneration, ischemia and inflammation. Bone marrow (BM)-derived haematopoietic stem cells (HSCs) are rare populations of multipotent stem cells that have been identified as promising potential candidates for treating a broad range of conditions. Although research into the use of stem cells for regenerative medicine is on a steep upward slope, clinical success has not been as forthcoming. This has been primarily attributed to a lack of information on the basic biology of stem cells, which remains insufficient to justify clinical studies. In particular, while our knowledge on the molecular adhesive mechanisms and local environmental factors governing stem cell homing to BM is detailed, our understanding of the mechanisms utilized at injured sites is very limited. For instance, it is unclear whether mechanisms used at injured sites are location specific or whether this recruitment can be modulated for therapeutic purposes. In addition, it has recently been suggested that platelets may play an important role in stem cell recruitment to sites of injury. A better understanding of the mechanisms used by stem cells during tissue homing would allow us to develop strategies to improve recruitment of these rare cells. This review will focus on the status of our current understanding of stem cell homing to injured tissues, the role of platelets and directions for the future.     

Influence of steroid drugs on orthodontically induced root resorption

OBJECTIVES: To investigate the effect of acute and chronic corticosteroid treatment on orthodontically induced root resorption. DESIGN: 'Split mouth' design performing orthodontic tooth movement in 64, 6-month-old male rats divided into three groups: acute (n = 22), chronic (n = 23) and control group (n = 19). Acute and chronic group received corticosteroid treatment (8 mg/kg/day) for 3 and 7 weeks, respectively, while no pharmacological treatment was performed in the control group. Performed at the Department of Orthodontics, School of Dentistry, University of Aarhus, Aarhus, Denmark. EXPERIMENTAL VARIABLE: The upper left first molar was moved mesially for 21 days in all three groups with 25 g of force. Undecalcified histological sections were cut at the coronal and apical level. OUTCOME MEASURE: The number of intersections hitting resorption lacunae (ES), defined as a scalloped surface with or without cementoclasts, over the total number of intersections hitting the root surface (RS) were recorded and expressed as percentage. RESULTS: The acute group showed significantly more root resorption at the mesio-coronal level compared with the control and the chronic group. CONCLUSION: This could be ascribed to the lack of balance between blastic activities (inhibited by the drug) and the clastic activities (enhanced or unchanged by drug administration) occurring in the initial phase of drug administration. As a consequence, a careful monitoring of patients undergoing acute corticosteroid treatment is suggested.     

Vaccine Related Reactogenicity for Primary Immunization: A Randomized Controlled Trial of 23(Wider) vs. 25(Narrower) Gauge Needles with Same Lengths

Objectives  

To compare vaccine related reactogenicity during primary immunization in healthy infants using 23 vs. 25 gauge needles.     

Personalized oncology: Recent advances and future challenges

Personalized oncology is evidence-based, individualized medicine that delivers the right care to the right cancer patient at the right time and results in measurable improvements in outcomes and a reduction on health care costs. Evolving topics in personalized oncology such as genomic analysis, targeted drugs, cancer therapeutics and molecular diagnostics will be discussed in this review. Biomarkers and molecular individualized medicine are replacing the traditional “one size fits all” medicine. In the next decade the treatment of cancer will move from a reactive to a proactive discipline. The essence of personalized oncology lies in the use of biomarkers. These biomarkers can be from tissue, serum, urine or imaging and must be validated. Personalized oncology based on biomarkers is already having a remarkable impact. Three different types of biomarkers are of particular importance: predictive, prognostic and early response biomarkers. Tools for implementing preemptive medicine based on genetic and molecular diagnostic and interventions will improve cancer prevention. Imaging technologies such as Computed Tomography (CT) and Positron Emitted Tomography (PET) are already influencing the early detection and management of the cancer patient. Future advances in imaging are expected to be in the field of molecular imaging, integrated diagnostics, biology driven interventional radiology and theranostics. Molecular diagnostics identify individual cancer patients who are more likely to respond positively to targeted chemotherapies. Molecular diagnostics include testing for genes, gene expression, proteins and metabolites. The use of companion molecular diagnostics is expected to grow significantly in the future and will be integrated into new cancer therapies a single (bundled) package which will provide greater efficiency, value and cost savings. This approach represents a unique opportunity for integration, increased value in personalized oncology.