Minimal clinically-important differences for the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) client-reported outcomes measures.

Client-reported outcomes measures (CROMs) have been previously validated for the evaluation of canine osteoarthritis. A published systematic review indicated that the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) can be recommended for use in dogs with osteoarthritis; these CROMs have also been used in the context of measuring surgical outcomes of dogs with orthopaedic conditions. However, the minimal clinically-important differences (MCIDs) for these CROMs have not been investigated. Such estimates would be useful for investigators and regulators so that these CROMs can be used in clinical trials. Data from the RCVS Knowledge Canine Cruciate Registry were extracted, and baseline and 6 week follow-up data on dogs that had received surgery for cranial cruciate ligament rupture were used to make estimates of MCIDs using distribution-based and anchor-based methods. Data from 125 dogs were categorised based on the anchor question and LOAD and COI scores analysed accordingly. The four anchor-based methods provided a range of MCIDs for each CROM (1 to 8.8 for LOAD and 3.5 to 17.6 for COI). In the two different distribution-based methods, the MCIDs for LOAD ranged from 1.5 (effect size) to 2.4 (standard error of measurement) and the effect size method yielded a result of 2.2 for COI. The results showed that the value of the MCIDs depended on the method that was applied. Receiver operator characteristic curves provided areas under the curve (AUCs) greater than 0.7, which indicated that the cut-off point was acceptable; LOAD had the greater AUC at 0.867. In summary, the authors currently recommend a MCID of '4' for LOAD and '14' for COI although further work in other clinical contexts (such as osteoarthritis associated with chronic pain) is required to add confidence to these estimates. For the first time, we have provided estimates for MCIDs for these two CROMs which will facilitate sample size estimates in future clinical studies that use these CROMs as outcomes measures.

Update on pulmonary embolism in pregnancy and post-partum: The Society of Obstetric Medicine of Australia and New Zealand Position Statement on Pulmonary Embolism in Pregnancy and Post-partum.

In this clinical review we highlight aspects of the diagnosis and management of pulmonary embolism (PE) in pregnancy and post-partum and how this may impact on antenatal and postnatal management. Investigation for PE in pregnancy is challenging and includes appropriate patient selection and knowledge of the risks and benefits of pulmonary imaging modalities. The complete Society of Obstetric Medicine of Australia and New Zealand Position Statement on Pulmonary Embolism in Pregnancy and Post-Partum comprehensively reviews all aspects of diagnosis, investigation and management and is accessible at https://www.somanz.org/guidelines.asp. It includes a summary of all recommendations and a guide to developing a management plan for birth in women on anticoagulation.

A zebrafish model of granulin deficiency reveals essential roles in myeloid cell differentiation.

Granulin is a pleiotropic protein involved in inflammation, wound healing, neurodegenerative disease, and tumorigenesis. These roles in human health have prompted research efforts to use granulin to treat rheumatoid arthritis and frontotemporal dementia and to enhance wound healing. But how granulin contributes to each of these diverse biological functions remains largely unknown. Here, we have uncovered a new role for granulin during myeloid cell differentiation. We have taken advantage of the tissue-specific segregation of the zebrafish granulin paralogues to assess the functional role of granulin in hematopoiesis without perturbing other tissues. By using our zebrafish model of granulin deficiency, we revealed that during normal and emergency myelopoiesis, myeloid progenitors are unable to terminally differentiate into neutrophils and macrophages in the absence of granulin a (grna), failing to express the myeloid-specific genes cebpa, rgs2, lyz, mpx, mpeg1, mfap4, and apoeb. Functionally, macrophages fail to recruit to the wound, resulting in abnormal healing. Our CUT&RUN experiments identify Pu.1, which together with Irf8, positively regulates grna expression. In vivo imaging and RNA sequencing experiments show that grna inhibits the expression of gata1, leading to the repression of the erythroid program. Importantly, we demonstrated functional conservation between the mammalian granulin and the zebrafish ortholog grna. Our findings uncover a previously unrecognized role for granulin during myeloid cell differentiation, which opens a new field of study that can potentially have an impact on different aspects of human health and expand the therapeutic options for treating myeloid disorders such as neutropenia or myeloid leukemia.

Use of romiplostim in pregnancy for refractory idiopathic thrombocytopenic purpura: Two case reports with maternal and fetal outcomes and literature review.

Idiopathic thrombocytopenic purpura is a relatively rare complication occurring in pregnancy, with the potential for serious maternal and fetal outcomes. Rarely, the poor response to established first-line therapies results in consideration of second-line therapies, which may have poorly understood risks to the fetus. We report two women with severe idiopathic thrombocytopenic purpura during pregnancy unresponsive to corticosteroids and intravenous immunoglobulin who were treated with romiplostim, a thrombopoietin receptor agonist. One woman with chronic idiopathic thrombocytopenic purpura had a partial response to romiplostim and suffered a post-partum haemorrhage related to uterine atony. The second woman developed severe idiopathic thrombocytopenic purpura in pregnancy and initially responded well to romiplostim. However, a lower segment Caesarean section was performed at 37 weeks for pre-eclampsia. The newborn suffered from severe idiopathic thrombocytopenic purpura and a grade 1 cerebral haemorrhage requiring intravenous immunoglobulin and platelet transfusions. Romiplostim might be a useful therapy for severe idiopathic thrombocytopenic purpura in pregnancy but requires further study.

Trypanosoma cruzi infection in a zoo-housed red panda in Kansas.

A 9-y-old, zoo-housed, male red panda (Ailurus fulgens) became progressively lethargic and inappetent over a 1-wk period. Physical examination was unremarkable. A complete blood count showed mild normocytic, normochromic, non-regenerative anemia with the presence of trypomastigote organisms, consistent with a Trypanosoma sp. The organism was confirmed later as Trypanosoma cruzi lineage TcI via PCR and genome sequencing. The panda was initially treated supportively; however, its clinical status within 24 h from presentation deteriorated, and euthanasia was elected. Autopsy showed severe systemic T. cruzi infection with the presence of amastigotes in the heart, brain, peripheral nerves, skeletal muscles, tongue, liver, and testes. We used genome sequencing and serology in identifying the agent.

Successful pregnancy in a recipient of an ABO-incompatible renal allograft.

Kidney transplantation restores fertility in patients with end-stage renal disease, with many successful pregnancies after kidney transplantation being reported. However, there are little data regarding pregnancy in women transplanted under modern-era desensitisation protocols that utilise rituximab, plasma exchange and intravenous immunoglobulin, including ABO-incompatible transplants. Pregnancies in ABO-incompatible recipients can pose new challenges from an immunological perspective. Here, we report a case of successful pregnancy using in vitro fertilisation, in a renal transplant recipient who underwent desensitisation two years prior, that included use of rituximab and plasma exchange to receive an ABO-incompatible transplant from her husband and subsequent father of the baby. We believe this was the first case of successful pregnancy after ABO-incompatible kidney transplantation in Australia and New Zealand. This case also highlights the difficulties faced in conception following transplantation and demonstrates that in vitro fertilisation utilising ovulation induction can be successfully utilised for conception in this cohort. This recipient also had gestational diabetes, worsening renal function and preterm delivery which are important complications often seen in pregnancies of solid organ transplant recipients.

SOMANZ guidelines for the investigation and management sepsis in pregnancy.

SOMANZ (Society of Obstetric Medicine Australia and New Zealand) has written a guideline to provide evidence-based guidance for the investigation and care of women with sepsis in pregnancy or the postpartum period. The guideline is evidence-based and incorporates recent changes in the definition of sepsis. The etiology, investigation and treatment of bacterial, viral and non-infective causes of sepsis are discussed. Obstetric considerations relevant to anaesthetic and intensive care treatment in sepsis are also addressed. A multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women have contributed to the development of the guidelines. This is an executive summary of the guidelines.

SOMANZ guidelines for the management of hypertensive disorders of pregnancy 2014.

This guideline is an evidence based, practical clinical approach to the management of Hypertensive Disorders of Pregnancy. Since the previous SOMANZ guideline published in 2008, there has been significant international progress towards harmonisation of definitions in relation to both the diagnosis and management of preeclampsia and gestational hypertension. This reflects increasing knowledge of the pathophysiology of these conditions, as well as their clinical manifestations. In addition, the guideline includes the management of chronic hypertension in pregnancy, an approach to screening, advice regarding prevention of hypertensive disorders of pregnancy, and discussion of recurrence risks and long term risk to maternal health. The literature reviewed included the previous SOMANZ Hypertensive Disorders of Pregnancy guideline from 2008 and its reference list, plus all other published National and International Guidelines on this subject. Medline, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Registry of Controlled Trials (CCRCT), National Institute for Health and Care Excellence (NICE) Evidence Search, and Database of Abstracts and Reviews of Effects (DARE) were searched for literature published between January 2007 and March, 2014.

Mechanical Testing of a Synthetic Canine Gastrocnemius Tendon Implant.

OBJECTIVE: To test a polyethylene terephthalate prosthesis (STIF, Chenove, France) for gastrocnemius tendon repair in dogs (cadaver model). STUDY DESIGN: In vitro mechanical study. ANIMALS: Pelvic limbs (n = 8) from 4 recently euthanatized adult dogs (weighing 30-45 kg). METHODS: Proximally the implant was sutured at the myotendinous junction of the gastrocnemius and distally secured in a 4.5 mm blind ending tunnel in the medullary cavity of the calcaneus using an interference screw (STIF, Chenove, France). Proximal and distal fixation were tested independently using an electrodynamic testing machine (Electropuls 3000, Instron, UK). RESULTS: Mean ± SD failure loads for the proximal fixation (266.13 ± 43.88 N) was significantly less than for the distal fixation (649.25 ± 210.36 N; P = .042, paired t-test). Mean stiffness of the proximal and distal constructs were 19.08 ± 8.16 N/mm and 139.76 ± 24.51 N/mm, respectively. CONCLUSIONS: Failure loads exceeded the values reported after experimental repair of chronic gastrocnemius tendon injuries using other methods involving suturing tendon to bone. Failure of this repair method clinically is predicted to occur proximally at the level of the myotendinous junction.

Transfer of metyrapone and its metabolite, rac-metyrapol, into breast milk.

Metyrapone, an inhibitor of corticosteroid biosynthesis, is used in the diagnosis and treatment of adrenocortical hyperfunction. The authors describe the excretion of metyrapone and its metabolite, rac-metyrapol, in milk from a lactating woman requiring metyrapone treatment (250 mg 4 times daily). At steady state, the average concentrations in milk and absolute and relative infant doses were 11 microg/L, 1.7 microg/kg/d, and 0.02%, respectively, for metyrapone, and 48.5 microg/L, 7.3 microg/kg/d, and 0.08%, respectively, for rac-metyrapol. The findings suggest that maternal metyrapone use during breastfeeding is extremely unlikely to be a significant risk for the breastfed infant.

Genetic susceptibility to viral exposure may increase the risk of cerebral palsy.

AIM: Cytokine polymorphisms may alter the fetal inflammatory response, increasing susceptibility to cerebral palsy (CP). This study investigates associations between selected inflammatory mediator and cytokine gene polymorphisms (Toll-like receptor-4 (TLR-4) Asp299Gly, interleukin-6 G-174C and interleukin-4 C-589T) and CP from 443 CP infants and 883 control infants. Results were correlated with viral nucleic acids in the same samples. RESULTS: At all gestational ages (GA), TLR-4 was associated with a decreased risk of developing CP (homozygous/heterozygous odds ratio (OR) 0.70, 95% confidence interval (CI) 0.50-0.98) and interleukin (IL)-6 was associated with an increased risk of developing hemiplegia (OR 1.38, 95% CI 1.05-1.83). For infants born 32-36 weeks GA, there was a tenfold increase in the risk of quadriplegic CP with homozygous/heterozygous IL-6 (OR 10.42, 95% CI 1.34-80.82). Viral exposure in combination with IL-4 in preterm infants was associated with a fourfold increased risk of quadriplegia (homozygous/heterozygous OR 4.25, 95% CI 1.21-14.95). In very preterm infants, the absence of detectable viral exposure in combination with IL-4 decreased the risk of developing CP (homozygous/heterozygous OR 0.31, 95% CI 0.13-0.76). CONCLUSION: Polymorphisms in TLR-4 may be associated with a decreased risk of CP. Polymorphisms in IL-6 or IL-4 may act as susceptibility genes, in the presence of viral exposure, for the development of hemiplegic and quadriplegic CP. These associations require confirmation but they suggest a hypothesis for CP causation due to double jeopardy from neurotropic viral exposure and genetic susceptibility to infection.

Increased delivery of haemodialysis assists successful pregnancy outcome in end-stage renal failure.

Pregnancy in patients on maintenance dialysis is rare, with few cases of successful live births reported in Australian women on dialysis at the time of conception. Increasing dialysis delivery may improve outcomes for both mother and foetus in this high-risk situation. We report a case of successful pregnancy outcome with the application of an intensive dialysis regimen.