Dietary sodium restriction specifically potentiates left ventricular ACE inhibition by zofenopril, and is associated with attenuated hypertrophic response in rats with myocardial infarction.

INTRODUCTION: In patients with myocardial infarction (MI)-induced heart failure, angiotensin-converting enzyme (ACE) inhibitors are proven effective therapy in inhibiting the progression towards overt heart failure. However, the prognosis in these patients is still very poor, and optimisation of therapy is warranted. The antihypertensive and renoprotective effects of ACE inhibitors (ACE-Is) can be substantially enhanced by dietary sodium restriction. In line with the latter, the aim of the present study was to explore whether dietary sodium restriction enhances the efficacy of ACE-I after MI. METHODS: Rats with MI-induced left ventricular (LV) dysfunction received ACE-I therapy with zofenopril (5.5 mg/kg/day orally), with or without dietary sodium restriction. ACE activity was measured in non-infarcted LV tissue, kidneys and plasma. Effects on cardiac hypertrophy were examined by means of organ weight/body weight ratios. After blood pressure (BP) measurements, functional consequences of therapy were evaluated as LV pressure development in isolated perfused hearts. RESULTS: Dietary sodium restriction alone had no effect on any of the measured parameters, whereas zofenopril alone significantly reduced plasma and kidney ACE activity, but not LV ACE activity, nor LV weight/body weight ratio. However, only when ACE-I therapy was combined with dietary sodium restriction was LV ACE activity significantly reduced. This effect was paralleled by inhibition of LV hypertrophy. BP was reduced after infarction, and further reduced by zofenopril, but not affected by dietary sodium. Neither treatment was associated with effects on the MI-induced reduction of LV function in vitro. CONCLUSIONS: Effects of ACE inhibition with zofenopril can be potentiated by additional dietary sodium restriction. However, these effects were tissue-specific, since LV, but not kidney or plasma, ACE activity was affected by the additional dietary sodium restriction. Effects on LV ACE activity were paralleled by reduced LV hypertrophy. Since the measured parameters did not indicate any adverse side-effects, dietary sodium restriction may provide a safe strategy to improve ACE-I efficacy in patients with infarction-induced LV dysfunction.     

Subpopulations of peripheral blood dendritic cells during chemotherapy of ovarian cancer

OBJECTIVES: Ovarian carcinoma (OVC) is often diagnosed at an advanced stage and requires effective chemotherapy as a first-line treatment. However, chemotherapy may be associated with significant side-effects, like nausea, vomiting, hair loss, cognitive dysfunction, fatigue and changes in sexual functioning. Leucopenia is one of the most common and dangerous side effects of chemotherapy. Little is known about possible effects of chemotherapy on dendritic cells (DCs) counts and function, although it is well documented that primary and secondary cell-mediated immune response are suppressed during this treatment. DESIGN: In this study we evaluated the myeloid and lymphoid DCs in the peripheral blood (PB) of 37 women with OVC before and after first-line based on platin and taxane chemotherapy, and in 24 healthy blood donors. Patients received 6 courses of treatment, administered at 21-day intervals. MATERIAL AND METHODS: The myeloid (M) and lymphoid (L) DCs were estimated by flow cytometry before and after 9th and 15th week of treatment. RESULTS: The percentage of both MDCs and LDCs was significantly lower (0.09% and 0.04%) in PB of patients with ovarian cancer comparing to healthy women (0.25% and 0.33%). The percentage of both, myeloid and lymphoid DCs after 9th and 15th week (0.08% vs 0.08% and 0.06% vs 0.08%) of chemotherapy did not differ from that found before treatment (0.09% and 0.04%). The Myeloid to Lymphoid DCs ratio was significantly lower in patients receiving chemotherapy.     

Clinician perspectives on clinical decision support systems in lung cancer: Implications for shared decision‐making

BackgroundLung cancer treatment decisions are typically made among clinical experts in a multidisciplinary tumour board (MTB) based on clinical data and guidelines. The rise of artificial intelligence and cultural shifts towards patient autonomy are changing the nature of clinical decision‐making towards personalized treatments. This can be supported by clinical decision support systems (CDSSs) that generate personalized treatment information as a basis for shared decision‐making (SDM). Little is known about lung cancer patients'' treatment decisions and the potential for SDM supported by CDSSs. The aim of this study is to understand to what extent SDM is done in current practice and what clinicians need to improve it.ObjectiveTo explore (1) the extent to which patient preferences are taken into consideration in non‐small‐cell lung cancer (NSCLC) treatment decisions; (2) clinician perspectives on using CDSSs to support SDM.DesignMixed methods study consisting of a retrospective cohort study on patient deviation from MTB advice and reasons for deviation, qualitative interviews with lung cancer specialists and observations of MTB discussions and patient consultations.Setting and ParticipantsNSCLC patients (N = 257) treated at a single radiotherapy clinic and nine lung cancer specialists from six Dutch clinics.ResultsWe found a 10.9% (n = 28) deviation rate from MTB advice; 50% (n = 14) were due to patient preference, of which 85.7% (n = 12) chose a less intensive treatment than MTB advice. Current MTB recommendations are based on clinician experience, guidelines and patients'' performance status. Most specialists (n = 7) were receptive towards CDSSs but cited barriers, such as lack of trust, lack of validation studies and time. CDSSs were considered valuable during MTB discussions rather than in consultations.ConclusionLung cancer decisions are heavily influenced by clinical guidelines and experience, yet many patients prefer less intensive treatments. CDSSs can support SDM by presenting the harms and benefits of different treatment options rather than giving single treatment advice. External validation of CDSSs should be prioritized.Patient or Public ContributionThis study did not involve patients or the public explicitly; however, the study design was informed by prior interviews with volunteers of a cancer patient advocacy group. The study objectives and data collection were supported by Dutch health care insurer CZ for a project titled ‘My Best Treatment’ that improves patient‐centeredness and the lung cancer patient pathway in the Netherlands.     

Last Marrow Standing: Bone Marrow Transplantation for Acquired Bone Marrow Failure Conditions

Paroxysmal nocturnal hemoglobinuria, aplastic anemia, and myelodysplastic syndrome are a spectrum of acquired marrow failure, having a common pathologic thread of both immune dysregulation and the development of abnormal hematopoiesis. Allogeneic hematopoietic cell transplantation plays a critical role in the treatment of these disorders and, for many patients, is the only treatment modality with demonstrated curative potential. In recent years, there have been many breakthroughs in the understanding of the pathogenesis of these uncommon disorders. The subsequent advances in non-transplant therapies, along with concurrent improvement in outcomes after hematopoietic cell transplantation, necessitate continual appraisal of the indications, timing, and approaches to transplantation for acquired marrow failure syndromes. We review here contemporary and critical new findings driving current treatment decisions.     

Risk factors for infection after liver transplantation

Infection is a common cause of morbidity and mortality after liver transplantation. Risk factors relate to transplantation factors, donor and recipient factors. Transplant factors include ischaemia-reperfusion damage, amount of intra-operative blood transfusion, level and type of immunosuppression, rejection, and complications, prolonged intensive care stay with dialysis or ventilation, type of biliary drainage, repeat operations, re-transplantation, antibiotics, antiviral regimen, and environment. Donor risk factors include infection, prolonged intensive care stay, quality of the donor liver (e.g. steatosis), and viral status. For the recipient the most important are MELD score >30, malnutrition, renal failure, acute liver failure, presence of infection or colonisation, and immune status for viruses like cytomegalovirus. In recent years it has become clear that genetic polymorphisms in innate immunity, especially the lectin pathway of complement activation and in Toll-like receptors importantly contribute to the infection risk after liver transplantation. Therefore, the risk for infections after liver transplantation is a multifactorial problem and all factors need attention to reduce this risk.     

The SMART‐COP score performs well for pneumonia risk stratification in Australia’s Tropical Northern Territory: a prospective cohort study

Objective To prospectively compare a modified pneumonia severity scoring system, SMARTACOP, with other severity scores in patients presenting with pneumonia to the emergency department (ED) of a tertiary referral hospital in tropical Australia. Methods We conducted a prospective observational study of adult patients presenting with radiologically confirmed pneumonia over a 12‐month period. The sensitivity of risk stratification scores were assessed against the need for intensive respiratory or vasopressor support (IRVS). Results There were 367 ED attendances for pneumonia of whom 77.1% were admitted to hospital, 10% required intensive respiratory or vasopressor support and 2.8% died. Mean age was 50.0 years, 52% were men and 59% were Indigenous. The sensitivity of a SMART‐COP score ≥3, a SMARTACOP score ≥3 and a pneumonia severity index (PSI) class ≥3 for predicting IRVS was 97%, 97% and 78% respectively. Conclusions We found no significant advantage of the SMARTACOP over the SMART‐COP score for the prediction of intensive respiratory or vasopressor support, but both scores significantly outperformed PSI. The SMART‐COP score should replace the PSI in tropical Australia and should be assessed in other tropical areas for pneumonia risk stratification in emergency departments.