Emerging Issues With Diagnosis and Management of Fungal Infections in Solid Organ Transplant Recipients

Invasive fungal infections (IFIs) are being increasingly recognized in solid organ transplant (SOT) recipients, and delayed diagnosis can lead to graft loss and death. Therefore, there is a low threshold for prophylaxis and early initiation of empiric antifungal treatment, in this patient population. Meanwhile, the increasing consumption of antifungals is associated with high cost, medication toxicities and the emergence of resistance in Candida species, all of which call for rational use of antifungal agents. The implementation of fungal biomarkers, molecular diagnostic methods and direct detection of volatile fungal metabolites in breath samples could lead to faster diagnosis, early appropriate treatment and improved clinical outcomes, but also aid in the de‐escalation of antifungal treatment. Those novel diagnostic modalities need to be validated specifically in SOT recipients. Infectious diseases consultation can contribute to optimization of care through prompt initiation and appropriate modification of antifungal treatment, management of medication toxicities and drug‐drug interactions, as well as source control. In this review, we conceptually summarize recent advances in the diagnosis and management of IFI in SOT recipients, and highlight the importance of early diagnostic tools and good stewardship of antifungal drugs.     

The Socioeconomic Impacts of Clinically Diagnosed Haemorrhagic Septicaemia on Smallholder Large Ruminant Farmers in Cambodia

Haemorrhagic septicaemia (HS) is an acute fatal infectious disease of mainly cattle and buffalo and outbreaks occur commonly in Cambodia. Disease outbreak reports were examined to select five villages from three provinces for a retrospective investigation of HS epidemiology and socioeconomic impact on smallholders, with an aim of identifying potential benefits from improving disease prevention through biosecurity and vaccination. The Village Animal Health Worker (VAHW) or Chief in each village and 66 affected smallholders were surveyed. At the village level, 24% of all households were affected with an estimated mean village herd morbidity of 10.1% and mortality of 28.8%. Affected farmers reported HS disease morbidity and mortality at 42.7% and 63.6% respectively. Buffalo had a higher morbidity (OR = 2.3; P = 0.003) and mortality (OR = 6.9; P < 0.001) compared with cattle, and unvaccinated large ruminants a higher morbidity (OR = 2.9; P = 0.001). The financial impact varied depending on whether the animal survived, provision of treatment, draught replacement and lost secondary income. The mean cost per affected household was USD 952.50 based on ownership of five large ruminants. The impact per affected animal was USD 375.00, reducing the pre‐disease value by 66.1%. A partial budget revealed an overwhelming incentive for farmers to practice biannual vaccination, with a net benefit of USD 951.58 per household based on an annual disease incidence rate of 1. Sensitivity analysis showed that a net benefit of USD 32.42 remained based on an outbreak every 20 years. This study indicates HS can cause a catastrophic financial shock to smallholders and remains a critical constraint to improving large ruminant productivity and profitability. Addressing HS disease control requires a focus on improving smallholder farmer knowledge of biosecurity and vaccination and should be priority to stakeholders interested in addressing regional food insecurity and poverty reduction.     

Long-term predictors for psychological outcome of pre-symptomatic testing for late-onset neurological diseases

This longitudinal study aimed at determining predicting variables for middle and long-term psychological disturbance due pre-symptomatic testing (PST) for two late-onset neurological diseases, Huntington disease (HD) and TTR (transthyretin protein) familial amyloid polyneuropathy (FAP) Val30Met (now classified as Val50Met). 196 clinical records of persons who performed PST at least three years ago and answered to the two stages of evaluation (before PST and least 3 years after disclosure of results) were analysed. For this purpose, regression analysis was performed, showing that the Positive Symptom Distress Index (PSDI), psychoticism, somatization and paranoid ideation dimensions assume predictive value in the middle and long-term impact for total anxiety and PSDI. The result of PST was not a relevant predictor. The application of an evaluation instrument of various psychopathological dimensions played a fundamental role in the detection of clinical situations that may arise several years later after PST. Attention should be paid to providing psychological support to persons at-risk who, at the pre-test phase, present some psychopathology indices before pursuing with genetic testing.     

Diffuse aspiration bronchiolitis: analysis of 20 consecutive patients

OBJECTIVE:

Aspiration can cause a variety of pulmonary syndromes, some of which are not well recognized. The objective of this study was to assess the demographic, clinical, radiological, and histopathological correlates of diffuse aspiration bronchiolitis (DAB), a bronchiolocentric disorder caused by recurrent aspiration.

METHODS:

This was a retrospective study of 20 consecutive patients with DAB seen at the Mayo Clinic in Rochester, Minnesota, between January 1, 1998 and June 30, 2014.

RESULTS:

The median age of the patients was 56.5 years (range, 22-76 years), and the male/female ratio was 2.3:1.0. In 18 patients, the diagnosis of DAB was based on the results of a lung biopsy; in the 2 remaining patients, it was based on clinical and radiological features, together with documented aspiration observed in a videofluoroscopic swallow study. In 19 patients (95%), we identified predisposing factors for aspiration, including gastroesophageal reflux disease (GERD), drug abuse, and dysphagia. Common presenting features included cough, sputum production, dyspnea, and fever. Twelve patients (60%) had a history of recurrent pneumonia. In all of the patients, chest CT revealed bilateral pulmonary infiltrates consisting of micronodules and tree-in-bud opacities. In the majority of patients, interventions aimed at preventing recurrent aspiration (e.g., anti-GERD therapies) led to improvement in the symptoms of DAB.

CONCLUSIONS:

Young to middle-aged subjects with recognizable predisposing factors for aspiration and who report a history of recurrent pneumonia are at increased risk for DAB. Although DAB is not well recognized, certain chest CT features are characteristic of the disorder.     

Measurement of coronary artery calcification with multi-slice spiral computed tomography and the associated factors in maintenance hemodialysis patients

Objective To investigate the factors correlated to coronary artery calcification (CAC) in maintenance hemodialysis (MHD) patients. Methods This study included 132 patients(54 females, 78 males), aged 26-94 years, who were on hemodialysis for 10-204 months(median dialysis duration 51.00 months). The parameters including calcium, phosphorus, parathyroid hormone, total cholesterol, low density lipoprotein, triglycerides, C - reactive protein (CRP), klotho, and so on were assessed. Quantification of CAC was determined by multi-slice spiral computed tomography (MSCT), known as the coronary artery calcification score (CACs). Results Ninety-two patients (69.70%) had CAC, with CACs ranging from 0 to 13 450.20. More than 30% patients experienced one even a variety of cardiovascular and cerebrovascular diseases. A positive correlation was observed between the degree of CAC and the incidence of cardiovascular and cerebrovascular diseases. Whereas a positive correlation existed between CACs and age (r=0.347, P=0.000), duration of hemodialysis (r=0.245, P= 0.005), systolic blood pressure (r=0.184, P=0.034), diabetes history (r=0.211, P=0.015), phosphorus (r= 0.262, P=0.002), calcium-phosphorus product (r=0.247, P=0.004); and a negative correlation between CACs and klotho level (r=-0.294, P=0.001). Multivariate logistic regression analysis showed that the main factor influencing the degree of CAC in MHD patients was age. Conclusions CAC is common and widespread in hemodialysis patients, who are often accompanied by cardiovascular and cerebrovascular diseases. The prevalence rate of cardiovascular and cerebrovascular diseases increases with the aggravation of CAC degree. Age, duration of hemodialysis, systolic blood pressure, diabetes history, disturbance of calcium and phosphorus metabolism and klotho are correlated with the severity of CAC. Age is an independent risk factor of CAC degree.     

Immunoglobulin shortage: Practice modifications and clinical outcomes in a reference centre

BackgroundGrowing numbers of indications for intravenous immunoglobulins (IVIg) in recent years has resulted in an increase in the consumption of these products. A lack of raw material has led to IVIg shortage. The objective of this work was to evaluate the impact of this situation on patient care in one French referral centre considering practice modifications and clinical impact.MethodsAll patients treated with IVIg for chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and myasthenia gravis from October 2017 to October 2018 were included.ResultsOut of 142 patients, 111 (78%) had a modification of their IVIg treatment. We noted that 75 (68%) patients had a delay in IVIg treatment, 41 (37%) patients had a decrease in IVIg doses and 31 (28%) experienced IVIg treatment interruption. Thirty percent of patients for whom IVIg treatment was discontinued were switched to other treatments mainly plasma exchange (16%) or corticosteroids (13%). Switches to plasma exchange or corticosteroids were carried out in order to save immunoglobulins for patients who had no other alternatives. Fifty-eight (52%) patients presented a deterioration of their clinical score after IVIg treatment changes including 31 (28%) patients who had a moderate or a clinically significant deterioration. Concerning practice modifications, we noted a substantial though not significant decrease in median IVIg dose for myasthenia gravis and a significant increase in the delay between IVIg courses for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy (P = 0.011 and P = 0.018 respectively).ConclusionOur study showed a rather important number of changes in IVIg treatment related to IVIg shortage during the period considered. These changes had a negative impact on the clinical status of some patients.     

Neuromyelitis optica spectrum disorders and systemic lupus erythematosus: A case series from a university center

Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory diseases of the central nervous system (CNS), which preferentially affect the optic nerves and the spinal cord. Anti-aquaporin 4 antibody is a specific serological marker. Systemic lupus erythematosus (SLE) is a rheumatologic disease that may affect the CNS. There are several reports about the coexistence of NMOSD and autoimmune diseases, mainly those of rheumatologic origin. We describe three different cases in which SLE and NMOSD subsequently occurred, drawing attention to the clinical heterogeneity, the challenge and the importance of recognizing this possible association.     

Estudio exploratorio sobre gastrostomía en pacientes con enfermedades neurológicas: utilidad e impacto

IntroductionPercutaneous endoscopic gastrostomy (PEG) is a useful intervention for patients with impaired swallowing and a functional gastrointestinal system. Neurological diseases that cause neuromotor dysphagia, brain tumors, and cerebrovascular disease are the most frequent indications; complications are rare, and morbidity and mortality rates are low.ObjectiveTo describe the usefulness of PEG in patients with neurological diseases, and its impact on care, survival, and costs and benefits.Material and methodsWe performed a retrospective observational study, reviewing clinical files of patients hospitalised at the National Institute of Neurology and Neurosurgery (years 2015-2017) who underwent PEG placement.ResultsThe sample included 51 patients: 62.7% were women and the mean (SD) age was 54.4 (18.6) years (range, 18-86). Diagnosis was tumor in 37.3% of cases and cerebrovascular disease in 33.3%. Sixteen patients (33.3%) died and 11 presented minor complications. The PEG tube remained in place for a mean of 9.14 months; in 52.9% of patients it was removed due to lack of improvement and/or tolerated oral intake, with removal occurring after a mean of 5.1 (4.4) months. Among patients’ family members, 78.4% reported a great benefit, 43.1% reported difficulty caring for the PEG, and 45.1% reported complicated care in general. The monthly cost of maintaining the PEG was €175.78 on average (range, 38.38-293.45).Discussion and conclusionsThis preliminary study reveals that PEG was well indicated in patients with neurological diseases, with survival rates similar to those reported in other studies with long follow-up periods. In patients with cerebrovascular disease, the PEG tube remained in place a mean of 9.14 months, during recovery of swallowing function; however, the cost is high for our population.