Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections

Introduction: Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site.

Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation.

Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy’s clinical positioning in the antimicrobial arsenal against RTIs.     

Comprehensive PKD1 and PKD2 Mutation Analysis in Prenatal Autosomal Dominant Polycystic Kidney Disease

Prenatal forms of autosomal dominant polycystic kidney disease (ADPKD) are rare but can be recurrent in some families, suggesting a common genetic modifying background. Few patients have been reported carrying, in addition to the familial mutation, variation(s) in polycystic kidney disease 1 (PKD1) or HNF1 homeobox B (HNF1B), inherited from the unaffected parent, or biallelic polycystic kidney and hepatic disease 1 (PKHD1) mutations. To assess the frequency of additional variations in PKD1, PKD2, HNF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were screened in 42 patients with early ADPKD in 41 families. Two patients were associated with de novo PKD1 mutations. Forty patients occurred in 39 families with known ADPKD and were associated with PKD1 mutation in 36 families and with PKD2 mutation in two families (no mutation identified in one family). Additional PKD variation(s) (inherited from the unaffected parent when tested) were identified in 15 of 42 patients (37.2%), whereas these variations were observed in 25 of 174 (14.4%, P=0.001) patients with adult ADPKD. No HNF1B variations or PKHD1 biallelic mutations were identified. These results suggest that, at least in some patients, the severity of the cystic disease is inversely correlated with the level of polycystin 1 function.     

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.     

Why do adults with palliative care needs present to the emergency department? A narrative review of the literature

Background: Given the increasing emphasis on community-based provision of palliative care and the view that good dying should occur at home, it is unsurprising that policy in many countries has started focusing on preventing hospital admissions at the end of life. However, little attention has been paid to the role of the emergency department (ED) in this regard, despite the fact that a high proportion of hospital admissions among patients with palliative care needs originate in the ED. This paper presents the next logical step in improving understanding of ED use within a palliative care context; as to determine what constitutes an avoidable ED presentation initially requires recognition of the reasons that such patients are presenting.

Methods: A systematic, narrative approach was used to appraise the relevant studies. From August to December 2014, electronic databases, gray literature and guidelines were searched, using MeSH headings and keywords. As it was anticipated that reasons for presentation would be differently described, all papers addressing presentations to the ED among patients with palliative care needs were identified; information regarding reasons for presentation were then examined.

Results: Twelve papers ultimately met the inclusion criteria and were accessible. The ‘reason’ for a patient's presentation was largely defined as their ‘presenting complaint’ or ‘underlying diagnosis.’ There was consistency in the studies in this respect; the majority found that people with lung cancer and those experiencing distressing respiratory symptoms were most likely the present to the ED. Subsequently, pain and gastrointestinal symptoms such as nausea and vomiting were uniformly found to be most common. The three prospective studies gathered information about reason for presentation from the patient perspective using structured questionnaires, but no study collected qualitative data from patients and families.

Discussion: This systematic narrative review is the first to explore reasons for ED presentation among patients with palliative care needs. However, the data does not facilitate a detailed discussion about the difficulties that this population of patients face, and whether they may be best managed in an acute or community setting. A deep understanding of the perspectives of patients is urgently needed, so as to both understand their reasons for presentation and implement relevant patient-directed changes in service provision.     

Matrix metalloproteinase expression patterns in luminal A type breast carcinomas

Objective: Aberrant expression of individual matrix metalloproteinases has been associated with poor prognosis in various human carcinomas. The current study aimed at defining an RNA expression profile of various MMPs in breast cancer and correlating their expression with clinicopathological parameters. Methods: The RNA expression patterns of 6 MMPs (MMP2, MMP8, MMP9, MMP10, MMP11, MMP13) were determined in 25 breast carcinomas using quantitative RT-PCR and correlated with clinicopathological parameters, including menopausal status, tumor size and grade, and lymph node involvement. Results: We observed high MMP2 levels more frequently in premenopausal than in postmenopausal women (p = 0.02). Analysis of luminal A type invasive ductal carcinomas (19/25), revealed an even stronger association of MMP2 with menopausal status (p = 0.005). Within this subgroup, we also found a correlation between MMP11 and menopausal status (p = 0.02). No correlation was found between MMP expressions and other clinicopathological parameters. In co-expression analyses MMP2-MMP10 and MMP8-MMP9 showed a weak correlation of their expression. Conclusions: Although this is a pilot study, our findings indicate that luminal A invasive ductal carcinomas commonly express high MMP2 and MMP11 levels in premenopausal breast cancer patients and suggest a co-regulation of MMP2-MMP10 and MMP8-MMP9.     

Extended spectrum of antibiotic susceptibility for tuberculosis,Djibouti

In the Horn of Africa, there is a high prevalence of tuberculosis that is reported to be partly driven by multidrug-resistant (MDR) Mycobacterium tuberculosis strictu sensu strains. We conducted a prospective study to investigate M. tuberculosis complex species causing tuberculosis in Djibouti, and their in vitro susceptibility to standard anti-tuberculous antibiotics in addition to clofazimine, minocycline, chloramphenicol and sulfadiazine. Among the 118 mycobacteria isolates from 118 successive patients with suspected pulmonary tuberculosis, 111 strains of M. tuberculosis, five Mycobacterium canettii, one ‘Mycobacterium simulans’ and one Mycobacterium kansasii were identified. Drug-susceptibility tests performed on the first 78 isolates yielded nine MDR M. tuberculosis isolates. All isolates were fully susceptible to clofazimine, minocycline and chloramphenicol, and 75 of 78 isolates were susceptible to sulfadiazine. In the Horn of Africa, patients with confirmed pulmonary tuberculosis caused by an in vitro susceptible strain may benefit from anti-leprosy drugs, sulfamides and phenicol antibiotics.     

The Effect of Media on Body Image in Pregnant and Postpartum Women

Much research has found that exposure to certain types of media portrayals of women can be related to body image concerns among women. The current paper focuses on the impact of certain messages on pregnant and postpartum women. These women are rarely examined in a media research context but are particularly vulnerable to body image concerns. This experimental study involved 192 pregnant or postpartum women who read a magazine containing glamorized media portrayals of pregnant/postpartum women or a control magazine. Pregnant women reported lower body image after only five minutes of exposure to the magazine with pregnant/postpartum women compared to the control group. There was no immediate effect on postpartum women. Implications for the media industry, health professionals, and women are discussed.     

Use of a case-mix approach to study the trends in the incidence of second primary cancers

Purpose

To analyze trends in second primary cancer (SPC) incidence by using a case-mix approach to standardize on first cancer site distribution.

Occupational exposure to textile dust and lung cancer risk: Results from the ICARE Study

Background

To investigate the association of lung cancer with occupational exposure to textile dust and specifically to cotton dust in the population‐based case‐control study ICARE.

Methods

Lifelong occupational history of 2926 cases and 3555 controls was collected using standardized questionnaires, with specific questions for textile dust exposure. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models controlling for confounding factors including smoking and asbestos exposure.

Results

An inverse association between textile dust exposure and lung cancer was found among workers exposed ≥5% of their work time (OR = 0.80, 95%CI = 0.58‐1.09), more pronounced for distant exposures (40+ years; up to a 56% reduced risk, statistically significant). The OR of lung cancer was significantly decreased among workers exposed to cotton fibers (OR = 0.70, 95%CI = 0.48‐0.97).

Conclusions

Our results provide some evidence of a decreased risk of lung cancer associated with exposure to textile dust, particularly cotton.