Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease.

Microbial transformation of bile acids affects intestinal immune homoeostasis but its impact on inflammatory pathologies remains largely unknown. Using a mouse model of graft-versus-host disease (GVHD), we found that T cell-driven inflammation decreased the abundance of microbiome-encoded bile salt hydrolase (BSH) genes and reduced the levels of unconjugated and microbe-derived bile acids. Several microbe-derived bile acids attenuated farnesoid X receptor (FXR) activation, suggesting that loss of these metabolites during inflammation may increase FXR activity and exacerbate the course of disease. Indeed, mortality increased with pharmacological activation of FXR and decreased with its genetic ablation in donor T cells during mouse GVHD. Furthermore, patients with GVHD after allogeneic hematopoietic cell transplantation showed similar loss of BSH and the associated reduction in unconjugated and microbe-derived bile acids. In addition, the FXR antagonist ursodeoxycholic acid reduced the proliferation of human T cells and was associated with a lower risk of GVHD-related mortality in patients. We propose that dysbiosis and loss of microbe-derived bile acids during inflammation may be an important mechanism to amplify T cell-mediated diseases.

Rethinking the need for a platelet transfusion threshold of 50 × 109 /L for lumbar puncture in cancer patients.

BACKGROUND: Lumbar puncture (LP) is a frequently performed diagnostic and therapeutic procedure in oncology patients. Transfusing to a minimum preprocedural platelet threshold of 50 × 109 /L is widely upheld without good quality evidence. The objective was to compare the outcomes of LPs performed with platelets above and below this threshold. An increased risk of adverse events in patients with lower platelet counts was not expected. As a corollary, transfusion reaction rates incurred by transfusing to this recommended threshold are also reported. METHODS: A total of 2259 LPs performed on 1137 oncology patients (adult, n = 871, and pediatric, n = 266) were retrospectively analyzed between February 2011 and December 2017. The incidence of LP-related complications for groups above and below the minimum platelet threshold was compared. Traumatic tap was defined as 500 or more red blood cells per high-power field in the cerebral spinal fluid. Groups were compared using the 2-Proportion Z-test and Fisher exact test. RESULTS: At time of LP, the total number of events with platelets less than 50 × 109 /L and 50 × 109 /L or greater were 110 and 2149, respectively. There were no significant differences in LP-associated complications between patients with platelet counts above or below 50 × 109 /L (P = .29). Patients with a pre-LP platelet count of less than 50 × 109 /L had a higher proportion of traumatic taps (P < .001). Three patients developed transfusion-related adverse events. CONCLUSION: Patients with platelet counts less than 50 × 109 /L did not have a higher incidence of clinically significant post-lumbar puncture complications (P = .29).

IPEM code of practice for high-energy photon therapy dosimetry based on the NPL absorbed dose calibration service.

The 1990 code of practice (COP), produced by the IPSM (now the Institute of Physics and Engineering in Medicine, IPEM) and the UK National Physical Laboratory (NPL), gave instructions for determining absorbed dose to water for megavoltage photon (MV) radiotherapy beams (Lillicrap et al 1990). The simplicity and clarity of the 1990 COP led to widespread uptake and high levels of consistency in external dosimetry audits. An addendum was published in 2014 to include the non-conventional conditions in Tomotherapy units. However, the 1990 COP lacked detailed recommendations for calibration conditions, and the corresponding nomenclature, to account for modern treatment units with different reference fields, including small fields as described in IAEA TRS483 (International Atomic Energy Agency (IAEA) 2017, Vienna). This updated COP recommends the irradiation geometries, the choice of ionisation chambers, appropriate correction factors and the derivation of absorbed dose to water calibration coefficients, for carrying out reference dosimetry measurements on MV external beam radiotherapy machines. It also includes worked examples of application to different conditions. The strengths of the 1990 COP are retained: recommending the NPL2611 chamber type as secondary standard; the use of tissue phantom ratio (TPR) as the beam quality specifier; and NPL-provided direct calibration coefficients for the user's chamber in a range of beam qualities similar to those in clinical use. In addition, the formalism is now extended to units that cannot achieve the standard reference field size of 10 cm × 10 cm, and recommendations are given for measuring dose in non-reference conditions. This COP is designed around the service that NPL provides and thus it does not require the range of different options presented in TRS483, such as generic correction factors for beam quality. This approach results in a significantly simpler, more concise and easier to follow protocol.

Clinical Performance of (1,3) Beta-D Glucan for the Diagnosis of Pneumocystis Pneumonia (PCP) in Cancer Patients Tested With PCP Polymerase Chain Reaction.

BACKGROUND: Serum (1,3)-beta-D glucan (BDG) is increasingly used to guide the management of suspected Pneumocystis pneumonia (PCP). BDG lacks specificity for PCP, and its clinical performance in high-risk cancer patients has not been fully assessed. Polymerase chain reaction (PCR) for PCP detection is highly sensitive, but cannot differentiate between colonization and infection. We evaluated the diagnostic performance of serum BDG in conjunction with PCP PCR on respiratory samples in patients with cancer and unexplained lung infiltrates. METHODS: We performed a retrospective analysis of adult patients evaluated for PCP at our institution from 2012 to 2015, using serum BDG and PCP PCR. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the serum BDG at different thresholds were evaluated using PCP PCR alone or in conjunction with clinical presentation in PCP PCR-positive patients. RESULTS: With PCP PCR alone as the reference method, BDG (≥80 pg/mL) had a sensitivity of 69.8%, specificity of 81.2%, PPV of 34.6%, and NPV of 95.2% for PCP. At ≥200 pg/mL in patients with a positive PCR and a compatible PCP clinical syndrome, BDG had a sensitivity of 70%, specificity of 100%, PPV of 100%, and NPV of 52.0% for PCP. CONCLUSIONS: Patients negative by both BDG and PCR were unlikely to have PCP. In patients with a compatible clinical syndrome for PCP, higher BDG values (>200 pg/mL) were consistently associated with clinically-significant PCP infections among PCP PCR-positive oncology patients.

IPEM topical report 1: guidance on implementing flattening filter free (FFF) radiotherapy.

Flattening filter free (FFF) beams are now commonly available with new standard linear accelerators. These beams have recognised clinical advantages in certain circumstances, most notably the reduced beam-on times for high dose per fraction stereotactic treatments. Therefore FFF techniques are quickly being introduced into clinical use. The purpose of this report is to provide practical implementation advice and references for centres implementing FFF beams clinically. In particular UK-specific guidance is given for reference dosimetry and radiation protection.

Tissue changes adjacent to titanium plates in patients.

INTRODUCTION: Titanium miniplates are widely used for osteosynthesis in maxillofacial surgery. Titanium is considered to be well tolerated but the long-term effects of titanium retained within human tissues are unclear. AIMS: This study was designed to evaluate histomorphologically the soft tissues adjacent to titanium maxillofacial miniplates and screws in patients, and to determine the nature of pigmented, particulate debris found in the tissues. MATERIALS: Thirty-five soft tissue specimens were excised from the tissues adjacent to titanium miniplates which had been in situ for between 1 month and 13 years. METHODS: All of the soft tissue specimens were prepared for examination under the light microscope. Four specimens were examined under the scanning electron microscope and the transmission electron microscope. Energy dispersive X-ray analysis (EDX) was used to confirm the elemental composition of the particles under investigation. RESULTS: All of the soft tissues showed fibrosis. Pigmented debris was present in 70% of the specimens and titanium was identified by EDX analysis. The debris was predominantly extra-cellular and was not associated with any inflammatory response or giant cell reaction. Fibroblasts were the predominant cell with small aggregates of lymphocytes and scattered macrophages. CONCLUSION: Titanium is apparently well tolerated for up to 13 years.

Laser em Odontologia / Lasers in Dentistry

Os autores apresentam um trabalho de atualização sobre o uso clínico do "laser" na Odontologia, com documentação fotográfica e especificações por especialidade

O uso do laser CO2 no tratamento de lesöes de tecidos moles da cavidade oral / The use of the CO2 laser in the treatment of injuries of soft tissue oral cavity

O uso do lase CO2 em cirurgia buco-maxilo-facial tem sido largamente descrito nos últimos cinco anos. Neste estudo, 70 pacientes com diversos tipos de patologias da cavidade oral tratados com o laser CO2 no período de 1985 a 1990, em Birminghan (Inglaterra), tiveram seus prontuários revistos. Os resultados deste estudo mostram que o uso do laser CO2 no tratamento de patologias da cavidade oral apresenta algumas vantagens sobre as técnicas convencionais. A efetiva reduçäo das complicaçöes pré e pós-operatórias resultaram em um menor período de internaçäo e reduçäo de custos. Desconforto local e dor moderada ou severa foram as queixas mais freqüentes após as cirurgias. Embora um caso de trismo, um caso de aprestesia transitória do lábio inferior e dois casos de infecçäo terem sido observados, parece-nos improvável que estas complicaçöes tenham sido um resultado direto da irradiaçäo laser. Esses resultados indicam que o uso do laser CO2 na cavidade oral é muito promissor, porém estudo adicionais säo ainda necessários, principalmente no tocante a respostas teciduais e procedimentos cirúrgicos envolvendo tecido ósseo