Pathobiology of Lomentospora prolificans: could this species serve as a model of primary antifungal resistance?

The number of fungal isolates resistant to antifungal drugs has increased dramatically over the last few years and has become an important concern for clinicians. Among these isolates, fungi showing multidrug resistance are particularly worrying because of the difficulties associated with their treatment. These factors hamper the successful recovery of patients and drastically raise mortality rates. Antifungal resistance is multifactorial and several mechanisms in different fungi have been described. There is a need to study these mechanisms in depth; however, the study of antifungal drug resistance separately for each individual species makes progress in the field very slow and tedious. The selection of a multiresistant microorganism as a model for understanding resistance mechanisms and extrapolating the results to other species could help in the search for a solution. In this mini-review, we describe the pathobiology of Lomentospora (Scedosporium) prolificans, paying special attention to its intrinsic resistance to all currently available antifungal agents. The characteristics of L. prolificans offer several advantages: the possibility of using a single microorganism for the study of resistance to different drugs, even cases of double and triple resistance; it is biologically safe for society in general as no new genetically–modified strains are needed for the experiments; it is homologous with other fungal species, and there is repetitiveness between different strains. In conclusion, we propose L. prolificans as a candidate for consideration as a fungal model for the study of resistance mechanisms against antifungal agents.     

Utilization of peritoneal dialysis in the United States: Reasons for underutilization,specifically in New York State and the boroughs of New York City

Peritoneal dialysis (PD) is currently underutilized in the United States (US), even within resource-rich neighborhoods. We analyzed data from US Renal Data Service to determine PD utilization within the US, New York State (NYS), selected boroughs within New York City (NYC), and Boston, Massachusetts. We then compared the odds of selecting PD with hemodialysis (HD) and analyzed how diabetes mellitus status, age >65 years, gender, and race influenced PD utilization between 2010 and 2016. We then compared a high-volume PD center (HVC) with a low-volume PD center (LVC). The odds of starting PD vs HD were as follows: Brooklyn 0.30 (0.25-0.36; <0.0001), Bronx 0.56 (0.47-0.67; <0.0001), Queens 0.66 (0.54-0.80; <0.0001), and Manhattan 0.61 (0.52-0.71; <0.0001). In 2016, the odds of starting PD compared with the rest of the US were as follows: Brooklyn 0.14 (0.08-0.22; <0.0001), Bronx 0.39 (0.27-0.56; <0.0001), Queens 0.32 (0.23-0.45; <0.0001), Manhattan 0.54 (0.36-0.79; 0.002), and Boston 0.89 (0.58-1.4; 0.624). Analysis of influencing factors showed that only age >65 significantly (<0.0001) influenced PD modality selection in Brooklyn and Boston. Differences between HVC and LVC in terms of modality transition, peritonitis rate, or provider:patient ratio were not statistically significant. Factors that influence PD utilization in urban neighborhoods are discussed and remediation measures are proposed.     

Advanced glycoxidation. A new risk factor for cardiovascular disease?

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. A large body of evidence both in vitro and in vivo suggests an important role for advanced glycoxidation end products (AGE) in the development or progression of CVD. AGE are a heterogenous group of molecules formed within the body during aging and, at an accelerated rate, in diabetes. AGE result from the nonenzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. Diet is considered an important exogenous source of highly reactive AGE. Recent studies have suggested a relationship between AGE and features of CVD. These findings together with the cardioprotective effects of anti-AGE agents demonstrate the causal relationship of AGE to the development and progression of CVD. Prospective outcome and controlled studies are needed to further support this relationship.     

Prevalence of cardiac amyloidosis among elderly patients with systolic heart failure or conduction disorders

Objective: Cardiac amyloid infiltration can lead to systolic heart failure (HF) or to conduction disorders (CD). Patients with transthyretin (ATTR) amyloidosis are particularly exposed. We sought to determine the prevalence of ATTR and AL among patients >60?years admitted with CD or unexplained systolic HF and increased wall thickness.

Materials and Methods: We studied 143 patients (57% males, 79?±?9?years) with HF (N?=?28) or CD requiring pacemaker implantation (N?=?115). In total, 139 (97%) patients (28 with HF and 111 with CD) underwent ^99mTc-DPD scintigraphy to detect ATTR, and 105 (73%; 19 HF and 86?CD) underwent AL screening.

Results: Five patients (4%; 95%CI:0–7%) exhibited wild-type ATTR (ATTRwt) amyloidosis, 2 (2%; 95%CI:0–4%) had CD and 3 (11%; 95%CI:0–23%) HF. No patient showed AL. The 2 ATTRwt patients with CD were previously asymptomatic, did not show classical ECG signs and exhibited mild LV hypertrophy with preserved LVEF. By contrast, all ATTRwt patients with HF had ECG and echocardiographic signs of amyloid. During a mean follow-up of 18?±?11?months, 3(60%) patients with ATTRwt amyloidosis (1?CD and 2 HF) and 14(10.4%) without died.

Conclusion: Prevalence of ATTRwt amyloidosis in patients with CD requiring pacemaker is low. Although, additional studies are needed, prevalence seems to be higher in elderly patients with systolic HF.     

A Synthetic Analog of Resveratrol Inhibits the Proangiogenic Response of Liver Sinusoidal Cells during Hepatic Metastasis

We utilized Fas21, a resveratrol analog, to modulate the function of hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) during the angiogenic phase of murine liver metastasis by B16 melanoma and 51b colorectal carcinoma. Preangiogenic micrometastases were treated with Fas21 (1 mg/kg/day) or vehicle during the development of intra-angiogenic tracts. Mice treated with Fas21 showed reduced liver tumor foci in both liver metastasis models. Micrometastases were classified immunohistochemically, as well as according to their position coordinates and connection to local microvasculature. The volume of liver occupied by sinusoidal-type foci, containing infiltrating angiogenic capillaries, decreased by ~50% in Fas21-treated mice compared to vehicle-treated ones in both tumor metastasis models. The volume of portal foci, containing peripheral neoangiogenesis within a discontinuous layer of myofibroblasts, was similar in all experimental groups in both tumor metastasis models, but displayed enhanced necrotic central areas devoid of angiogenesis following Fas21 treatment. As a result, sinusoidal tumors from mice treated with Fas21 showed a 50% reduction in desmin(+)/asma(+) HSCs and CD31(+) vessel density, and a 45% reduction in intrametastatic VEGF mRNA compared with sinusoidal tumors from vehicle-treated mice. Necrotic portal metastases increased 2-4-fold in treated mice. In vitro, Fas21 reduced VEGF secretion by HSCs and 51b cells dose-dependently. Additionally, HSCs migration in response to tumor soluble factors was dose-dependently diminished by Fas21, as was LSEC migration in response to HSCs and tumor soluble factors. Resveratrol analog Fas21 inhibits the proangiogenic response of HSCs and LSECs during the development of murine liver metastasis.     

Analysis of KCNH2 and CACNA1C schizophrenia risk genes on EEG functional network modulation during an auditory odd-ball task

European Archives of Psychiatry and Clinical Neuroscience - A deficit in task-related functional connectivity modulation from electroencephalogram (EEG) has been described in schizophrenia. The use...     

Obese and non-obese hemodialysis patients have a similar prevalence of functioning arteriovenous fistula using pre-operative vein mapping

AIMS: The arteriovenous fistula (AVF) is the preferred hemodialysis access. Subset analyses of both the HEMO and DOPPS studies have shown that obese hemodialysis patients have a lower prevalence of functioning AVF. Doppler ultrasound may increase the prevalence of functioning AVF in obese subjects. PATIENTS AND METHODS: The effect of pre-operative vein mapping employed between 10/01/98 and 12/08/00 on the prevalence of functioning AVF in a single university hemodialysis program was studied. Preoperative ultrasound was performed to study venous and arterial systems on both arms. RESULTS: There were 50 obese patients, defined as bodymass index (BMI) > or = 27 kg/m2, and 130 patients with a lower BMI. The groups were similar in mean age and diabetes prevalence. The obese group had statistically significantly more females 34/50 versus 61/130 with p = 0.01. There was no statistically significant difference between the vein mapping parameters studied in the two BMI groups, including mean mid-forearm cephalic vein diameter, distal radial artery peak systolic velocity and subclavian vein patency. No obese patient required venography. There was no significant difference between the number of functioning AVF in both groups (22/50 obese, 48/130 lower BMI, p = 0.24). CONCLUSIONS: Pre-operative vein mapping is associated with a similar prevalence of functioning AVF in obese and lower BMI patients. Pre-operative ultrasound screening is a useful tool to promote AVF placement in obese patients.     

Vascular screening prior to placement of tunnelled and cuffed hemodialysis catheters

Purpose: To demonstrate the importance of venous vascular screening before the placement of tunneled and cuffed hemodialysis catheters in patients requiring hemodialysis prior to placement and/or maturation of an arteriovenous fistula (AVF) or graft (AVG). Methods: Between October 1998 and March 2000, all patients requiring hemodialysis access placement were prospectively evaluated with duplex ultrasound for status of upper extremity vessels and central veins prior to selection of a permanent access site. When interim tunneled and cuffed hemodialysis catheters were required, they were placed on the side contralateral to proposed AVF/AVG placement. No catheters were placed without initial vascular screening. The study group was compared to historical controls during a similar period (April 1997 through September 1998) when no vascular screening was performed. Results: During the study period, 234 screening duplex ultrasound examinations were performed in 244 patients. Ten patients required no screening prior to access site placement. Overall, 353 catheters were placed, 243 (69%) on the right side and 110 (31%) on the left side. During the control period, 394 catheters were placed in 255 patients, 306 (78%) right-sided and 88 (22%) left-sided. The increase in left-sided catheters with ultrasound screening and careful planning for future access sites was significant (p<0.01). Conclusion: Vascular-screening-directed catheter placement significantly alters the side of catheter placement when compared to a management protocol without prior screening. Such screening helps identify the side of permanent access placement, while directing interim catheters to the contralateral side such that central veins may be preserved for permanent access.