Karolinska Institutet

About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Cancer. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.

Short-Term Antibiotic Treatment Has Differing Long-Term Impacts on the Human Throat and Gut Microbiome

Abstract: Antibiotic administration is the standard treatment for the bacterium Helicobacter pylori, the main causative agent of peptic ulcer disease and gastric cancer. However, the long-term consequences of this treatment on the human indigenous microbiota are relatively unexplored. Here we studied short- and long-term effects of clarithromycin and metronidazole treatment, a commonly used therapy regimen against H. pylori, on the indigenous microbiota in the throat and in the lower intestine. The bacterial compositions in samples collected over a four-year period were monitored by analyzing the 16S rRNA gene using 454-based pyrosequencing and terminal-restriction fragment length polymorphism (T-RFLP). While the microbial communities of untreated control subjects were relatively stable over time, dramatic shifts were observed one week after antibiotic treatment with reduced bacterial diversity in all treated subjects in both locations. While the microbiota of the different subjects responded uniquely to the antibiotic treatment some general trends could be observed; such as a dramatic decline in Actinobacteria in both throat and feces immediately after treatment. Although the diversity of the microbiota subsequently recovered to resemble the pre treatment states, the microbiota remained perturbed in some cases for up to four years post treatment. In addition, four years after treatment high levels of the macrolide resistance gene erm(B) were found, indicating that antibiotic resistance, once selected for, can persist for longer periods of time than previously recognized. This highlights the importance of a restrictive antibiotic usage in order to prevent subsequent treatment failure and potential spread of antibiotic resistance.

EFNS guidelines on pharmacological treatment of neuropathic pain

Abstract: Neuropathic pain treatment remains unsatisfactory despite a substantial increase in the number of trials. This EFNS Task Force aimed at evaluating the existing evidence about the pharmacological treatment of neuropathic pain. Studies were identified using first the Cochrane Database then Medline. Trials were classified according to the aetiological condition. All class I and II controlled trials (according to EFNS classification of evidence) were assessed, but lower-class studies were considered in conditions that had no top level studies. Only treatments feasible in an outpatient setting were evaluated. Effects on pain symptoms/signs, quality of life and comorbidities were particularly searched for. Most of the randomized controlled trials included patients with postherpetic neuralgia (PHN) and painful polyneuropathies (PPN) mainly caused by diabetes. These trials provide level A evidence for the efficacy of tricyclic antidepressants, gabapentin, pregabalin and opioids, with a large number of class I trials, followed by topical lidocaine (in PHN) and the newer antidepressants venlafaxine and duloxetine (in PPN). A small number of controlled trials were performed in central pain, trigeminal neuralgia, other peripheral neuropathic pain states and multiple-aetiology neuropathic pains. The main peripheral pain conditions respond similarly well to tricyclic antidepressants, gabapentin, and pregabalin, but some conditions, such as HIV-associated polyneuropathy, are more refractory. There are too few studies on central pain, combination therapy, and head-to-head comparison. For future trials, we recommend to assess quality of life and pain symptoms or signs with standardized tools.

Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series,

Abstract: Purpose: Recently, a 76-gene prognostic signature able to predict distant metastases in lymph node–negative (N − ) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment. Experimental Design: Gene expression profiling of frozen samples from 198 N − systemically untreated patients was done at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. Survival analyses, done by an independent statistician, were done with the genomic risk and adjusted for the clinical risk, defined by Adjuvant! Online. Results: The actual 5- and 10-year time to distant metastasis were 98% (88-100%) and 94% (83-98%), respectively, for the good profile group and 76% (68-82%) and 73% (65-79%), respectively, for the poor profile group. The actual 5- and 10-year overall survival were 98% (88-100%) and 87% (73-94%), respectively, for the good profile group and 84% (77-89%) and 72% (63-78%), respectively, for the poor profile group. We observed a strong time dependence of this signature, leading to an adjusted hazard ratio of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for time to distant metastasis and overall survival, respectively. Conclusion: This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.

Association of class I major histocompatibility heavy and light chains induced by viral peptides.

Abstract: We describe a cell in which association of a major histocompatibility complex class I heavy chain with beta 2-microglobulin is induced by a peptide derived from influenza nucleoprotein. Association of antigenic peptides with the binding site of class I molecules may be required for correct folding of the heavy chain, association with beta 2-microglobulin and transport of the antigen-MHC complex to the cell surface.

A systematic review of the incidence of biological and technical complications in implant dentistry reported in prospective longitudinal studies of at least 5 years

Abstract: Objective: To systematically review the incidence of biological and technical complications in implant therapy reported in prospective longitudinal studies of at least 5 years. Methods: A MEDLINE search was conducted for prospective longitudinal studies with follow-up periods of at least 5 years. Screening and data abstraction were performed independently by multiple reviewers. The types of complications assessed were as follows: implant loss, sensory disturbance, soft tissue complications, peri-implantitis, bone loss ≥2.5 mm, implant fracture and technical complications related to implant components and suprastructures. Results: The search provided 1310 titles and abstracts, out of which 159 were selected for full-text analysis. Finally, 51 studies were included. Meta analysis of these studies indicated that implant loss prior to functional loading is to be expected to occur in about 2.5% of all implants placed in implant therapy including more than one implant and when routine procedures are used. Implant loss during function occurs in about 2–3% of implants supporting fixed reconstructions, while in overdenture therapy >5% of the implants can be expected to be lost during a 5-year period. Few studies (41% of those included) reported data on the incidence of persisting sensory disturbance >1 year following implant surgery. Most of the studies that provided such data reported on the absence or a low incidence (1–2%) of this complication beyond this interval. A higher incidence of soft tissue complications was reported for patients treated with implants supporting overdentures. There is limited information regarding the occurrence of peri-implantitis and implants exhibiting bone loss ≥2.5 mm. Implant fracture is a rare complication and occurs in <1% of all implants during a 5-year period. The incidence of technical complications related to implant components and suprastructures was higher in overdentures than in fixed reconstructions. Conclusion: Implant loss was most frequently described (reported in about 100% of studies), while biological complications were considered in only 40–60% and technical complications in only 60–80% of the studies. This observation indicates that data on the incidence of biological and technical complications may be underestimated and should be interpreted with caution.