Therapeutic applications of lysostaphin against Staphylococcus aureus.

Staphylococcus aureus, an opportunistic pathogen, causes diverse community and nosocomial-acquired human infections, including folliculitis, impetigo, sepsis, septic arthritis, endocarditis, osteomyelitis, implant-associated biofilm infections and contagious mastitis in cattle. In recent days, both methicillin-sensitive and methicillin-resistant S. aureus infections have increased. Highly effective anti-staphylococcal agents are urgently required. Lysostaphin is a 27 kDa zinc metallo antimicrobial lytic enzyme that is produced by Staphylococcus simulans biovar staphylolyticus and was first discovered in the 1960s. Lysostaphin is highly active against S. aureus strains irrespective of their drug-resistant patterns with a minimum inhibitory concentration of ranges between 0·001 and 0·064 µg ml-1 . Lysostaphin has activity against both dividing and non-dividing S. aureus cells; and can seep through the extracellular matrix to kill the biofilm embedded S. aureus. In spite of having excellent anti-staphylococcal activity, its clinical application is hindered because of its immunogenicity and reduced bio-availability. Extensive research with lysostaphin lead to the development of several engineered lysostaphin derivatives with reduced immunogenicity and increased serum half-life. Therapeutic efficacy of both native and engineered lysostaphin derivatives was studied by several research groups. This review provides an overview of the therapeutic applications of native and engineered lysostaphin derivatives developed to eradicate S. aureus infections.

Impregnation of catheters with anacardic acid from cashew nut shell prevents Staphylococcus aureus biofilm development.

AIM: The effect of anacardic acid impregnation on catheter surfaces for the prevention of Staphylococcus aureus attachments and biofilm formations were evaluated. METHODS AND RESULTS: Silicon catheter tubes were impregnated using different concentrations of anacardic acids (0·002-0·25%). Anacardic acids are antibacterial phenolic lipids from cashew nut (Anacardium occidentale) shell oil. Anacardic acid-impregnated silicon catheters revealed no significant haemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of anacardic acids was observed for 4 days. Anacardic acid-impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo antibiofilm activity of anacardic acid-impregnated catheters was tested in an intraperitoneal catheter-associated medaka fish infection model. Significant reduction in S. aureus colonization on anacardic acid-impregnated catheter tubes was observed. CONCLUSIONS: Our data suggest that anacardic acid-impregnated silicon catheters may help in preventing catheter-related staphylococcal infections. SIGNIFICANCE AND IMPACT OF THE STUDY: This study opens new directions for designing antimicrobial phytochemical-coated surfaces with ideal antibiofilm properties and could be of great interest for biomedical research scientists.

Invasive mould sinusitis in patients with haematological malignancies: a 10 year single-centre study.

OBJECTIVES: Invasive mould sinusitis (IMS) is a severe infection in patients with haematological malignancies. Because of a paucity of contemporaneous data about IMS, we sought to evaluate clinical aspects and outcome of IMS in these patients. METHODS: The records of adult haematological malignancy patients with proven or probable IMS over a 10 year period were reviewed retrospectively. RESULTS: We identified 44 patients with IMS. Mucorales were isolated in 13 (35.1%) patients and Fusarium and Aspergillus were isolated in 9 (24.3%) patients each. Patients with IMS owing to Mucorales were more likely to have a history of diabetes mellitus (P = 0.003) and high-dose corticosteroid use (P = 0.03). Thirty-five (80%) patients received antifungal combinations and 36 (82%) underwent surgical debridement. The 12 week IMS-attributable mortality was 36.4% (16 patients). A relapsed and/or refractory haematological malignancy was an independent risk factor for 6 week IMS-attributable (P = 0.038), 12 week all-cause (P = 0.005) and 12 week IMS-attributable (P = 0.0015) mortality. Neutrophil count <100/µL and lymphocyte count <200/µL were associated with increased 12 week IMS-attributable and 6 week all-cause mortality, respectively (P = 0.044 and 0.013). IMS due to Aspergillus was an independent risk factor for both 12 week all-cause (P = 0.011) and IMS-attributable (P = 0.026) mortality. Initial antifungal therapy with a triazole-containing regimen was associated with decreased 6 week all-cause (P = 0.032) and IMS-attributable (P = 0.038) mortality. Surgery was not an independent factor for improved outcome. CONCLUSIONS: Despite combined medical and surgical therapy, IMS had high mortality. Mortality risk factors were relapsed and/or refractory malignancy, cytopenia and Aspergillus infection in this study.

Recommended Resting-State fMRI Acquisition and Preprocessing Steps for Preoperative Mapping of Language and Motor and Visual Areas in Adult and Pediatric Patients with Brain Tumors and Epilepsy.

Resting-state (rs) fMRI has been shown to be useful for preoperative mapping of functional areas in patients with brain tumors and epilepsy. However, its lack of standardization limits its widespread use and hinders multicenter collaboration. The American Society of Functional Neuroradiology, American Society of Pediatric Neuroradiology, and the American Society of Neuroradiology Functional and Diffusion MR Imaging Study Group recommend specific rs-fMRI acquisition approaches and preprocessing steps that will further support rs-fMRI for future clinical use. A task force with expertise in fMRI from multiple institutions provided recommendations on the rs-fMRI steps needed for mapping of language, motor, and visual areas in adult and pediatric patients with brain tumor and epilepsy. These were based on an extensive literature review and expert consensus.Following rs-fMRI acquisition parameters are recommended: minimum 6-minute acquisition time; scan with eyes open with fixation; obtain rs-fMRI before both task-based fMRI and contrast administration; temporal resolution of ≤2 seconds; scanner field strength of 3T or higher. The following rs-fMRI preprocessing steps and parameters are recommended: motion correction (seed-based correlation analysis [SBC], independent component analysis [ICA]); despiking (SBC); volume censoring (SBC, ICA); nuisance regression of CSF and white matter signals (SBC); head motion regression (SBC, ICA); bandpass filtering (SBC, ICA); and spatial smoothing with a kernel size that is twice the effective voxel size (SBC, ICA).The consensus recommendations put forth for rs-fMRI acquisition and preprocessing steps will aid in standardization of practice and guide rs-fMRI program development across institutions. Standardized rs-fMRI protocols and processing pipelines are essential for multicenter trials and to implement rs-fMRI as part of standard clinical practice.

Thoracolumbar curve and Cobb angle in determining spread of spinal anesthesia in Scoliosis. An observational prospective pilot study.

BACKGROUND AND AIMS: Disparity in spread of spinal anesthesia is a known complication in scoliosis patients. Our primary aim was to compare this disparity based on Cobb Angle and thorocolumbar spine curvature. Secondary aim was to calculate the appropriate lateral angulation of the spinal needle from midline for successful lumbar puncture. MATERIALS AND METHODS: All poliomyelitis patients with scoliosis posted for lower limb orthopedic contracture release surgeries were enrolled into Group A (Cobb Angle <50°), Group B (Cobb Angle >50°), and on thoracolumbar curve into Group R (Right), Group L (Left). Group A, B, R, and L were studied for bilateral spread of spinal anaesthesia. Lateral angle of the spinal needle from midline was noted with Goniometer in groups A and B. Statistical analysis was done using unpaired t test and Chi-square test. RESULTS: Failures in subarachnoid block (SAB) (unilateral anaesthesia/inadequate/patchy block) was significant in Group B (P = 0.033). Segmental disparity in bilateral spread of spinal anaesthesia was significant in Group R with P value of 0.042. Approximate lateral angle for needle in Group A was (4.1 ± 2.45) and in Group B was (9.14 ± 2.45). CONCLUSIONS: The study showed that there was a strong correlation between right-sided thoracolumbar curve and the spread of spinal anesthesia.

Dynamic Contrast-Enhanced MRI in Patients with Brain Metastases Undergoing Laser Interstitial Thermal Therapy: A Pilot Study.

BACKGROUND AND PURPOSE: Tumor recurrence is difficult to predict in patients receiving laser ablation for intracranial malignancy. We assessed the efficacy of the initial area under the time-to-signal intensity curve at 60 seconds (iAUC60) from dynamic contrast-enhanced MR imaging in predicting progression-free survival in patients with brain metastases following laser interstitial thermal therapy. MATERIALS AND METHODS: The study population was a consecutive series of patients undergoing laser interstitial thermal therapy for brain metastases. Patient demographics including age, sex, tumor histology, and Karnofsky Performance Scale were collected prospectively. Preoperative, postoperative, and 1-month follow-up dynamic contrast-enhanced MRIs were analyzed. Values of iAUC60 were computed using a trapezoidal rule applied to the time history of contrast uptake over the first 60 seconds postenhancement. The change in iAUC60 (ΔiAUC60) was calculated by taking the difference between the values of iAUC60 from 2 time points. Pearson correlation coefficients were calculated between progression-free survival, defined as the time from laser interstitial thermal therapy to tumor recurrence, and iAUC60 or ΔiAUC60 values. RESULTS: Thirty-three cases of laser interstitial thermal therapy for 32 brain metastases in a cohort of 27 patients were prospectively analyzed. A significant relationship was observed between the values of iAUC60 from postoperative dynamic contrast-enhanced MR imaging and progression-free survival with Pearson correlation (P = .03) and Cox univariate analysis (P = .01). The relationship between preoperative and 1-month follow-up dynamic contrast-enhanced MR imaging was not significantly correlated with progression-free survival. Similarly, no statistically significant relationship was observed with ΔiAUC60 and progression-free survival between any time points. CONCLUSIONS: Progression-free survival is difficult to predict in patients undergoing laser interstitial thermal therapy for brain metastases due to confounding with posttreatment change. iAUC60 extracted from postoperative dynamic contrast-enhanced MR imaging shows promise for accurately prognosticating patients following this operative therapy.

Clinical presentation and outcome after anterior cervical discectomy and fusion for degenerative cervical disc disease.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) is a well-described surgical approach for symptomatic degenerative cervical disc disease which does not respond to conservative management. In the present study, we assessed clinical presentation and outcomes of ACDF. MATERIALS AND METHODS: The present study was conducted from October 1, 2015, to October 31, 2017, in the Department of Neurosurgery, Narayana Medical College and Hospital, Nellore, Andhra Pradesh, among 100 consecutive adult patients who underwent single- or two-level ACDF for degenerative cervical disc disease. RESULTS: The mean age was 47.2 ± 12.8 years (range: 20-74 years). Majority of the patients were male (86/100). Presenting symptoms were neck pain (77%), limb weakness (73%), paresthesias (53%), radicular pain (49%), stiffness in limbs (16%), and bladder involvement (13%). Fusion was done with stand-alone titanium cage/bone graft or titanium cage/bone graft with anterior cervical plate. At the time of discharge, significant improvement in preoperative symptoms (neck pain [47/77-61%], radicular pain [31/49-63%], limb weakness [53/73-72.6%], paresthesias [44/53-83%], stiffness in limbs [13/16-81%], and bladder symptoms [8/13-61%]) was reported by majority of these patients. Majority of these patients also reported improvement in preoperative sensory deficits at the time of discharge. Postoperative complications were hoarseness of voice (22%), dysphagia (16%), deterioration of motor power (8%), and postoperative hematoma (7%). CONCLUSIONS: A significant proportion of patients with degenerative cervical disc disease show remarkable recovery after ACDF.

CT assessment of vocal cord medialization.

BACKGROUND AND PURPOSE: Unilateral vocal cord paralysis (UVCP) occurs after iatrogenic injury or disease process and is associated with dysphonia and aspiration. Various surgical options are available for treatment of UVCP, including vocal cord medialization thyroplasty and injection laryngoplasty. These augmentative procedures improve phonation and airway protection. Our purpose was to demonstrate the CT appearance of implants used for the treatment of UVCP. METHODS: Twelve patients treated surgically for UVCP were studied with helical CT. The vocal cords were augmented by using Silastic implants (n = 7), polytetrafluoroethylene (Gore-Tex) implants (n = 2), Teflon injections (n = 2), or fat injection (n = 1). Augmented vocal cords were characterized by size, shape, and Hounsfield units (HU). Two other patients with failed medialization thyroplasty were evaluated for the position of the extruded implant relative to the paralyzed vocal cord. RESULTS: The 7 Silastic implants were triangular and hyperattenuated (293.4 +/- 90.4 HU). The 2 Gore-Tex implants were heterogeneous with lobulated medial margins and were hyperattenuating (320 and 414 HU). The injected materials demonstrated ovoid/masslike configurations: the 2 Teflon injections were hyperattenuated (107 and 429 HU), and the fat injection was hypoattenuated (-102 HU). Inferior displacement of the implant was demonstrated relative to the true vocal cord in 2 patients with failed Silastic thyroplasties. CONCLUSION: CT can distinguish various types of vocal cord augmentation. Silastic implants are recognized by their characteristic triangular configuration. The Gore-Tex implants had unique heterogeneous attenuation with lobulated medial margins. Fat and Teflon injections both appear ovoid/masslike. Teflon injection should not be mistaken for tumor.

Imaging Features of Malignant Lacrimal Sac and Nasolacrimal Duct Tumors.

The purpose of this study was to present the imaging features of primary and secondary malignant lacrimal sac and nasolacrimal duct tumors and their pattern of tumor spread in 18 patients. The most common tumor histology in our series was squamous cell carcinoma. In 15/18 patients, tumor involved both the lacrimal sac and duct at the time of diagnosis. In 11/16 patients on CT, the nasolacrimal bony canal was smoothly expanded without erosive changes. The medial canthus region (16/18) was a frequent site of direct tumor spread. Two patients had intraconal orbital spread of tumor. Tumor spread to the sinus or nasal cavity was observed in 5/13 primary tumors. Only 1 patient presented with nodal metastasis. There was no intracranial tumor extension, perineural tumor spread along the infraorbital nerve, distant metastasis, or dacryocystocele formation in any of the patients at the time of diagnosis.

Targeted biological therapies reach the heart: the case of serelaxin for heart failure.

Acute heart failure (AHF) is one of the most important causes of mortality, morbidity and rising healthcare costs. Despite this, there has been minimal advancement in the management of AHF and the treatment continues to focus on symptomatic improvement using vasodilators, diuretics and inotropes, none of which have shown any mortality benefits. Though originally thought of as a reproductive hormone, relaxin is now recognized as a potent vasodilator that modulates systemic and renal vascular tone, resulting in pre- and after-load reduction and a decrease in cardiac workload. A single intravenous infusion of relaxin over 48 hours has been shown to provide significant dyspnea relief among AHF patients, with an ongoing study to evaluate its potential for mortality benefit. This article provides an insight into the pharmacology of this novel therapy for AHF with an eye towards future clinical applications.

Extended daily dialysis: A new approach to renal replacement for acute renal failure in the intensive care unit.

Continuous venovenous hemofiltration (CVVH) is an effective form of renal replacement therapy for acute renal failure (ARF) that offers greater hemodynamic stability and better volume control than conventional hemodialysis in the critically ill, hypotensive patient. However, the application of CVVH in the intensive care unit (ICU) has several disadvantages, including intensive nursing requirements, continuous anticoagulation, patient immobility, and expense. We describe a new approach to the treatment of ARF in the ICU, which we have termed extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42 patients: 25 patients were treated with EDD for a total of 367 treatment days, and 17 patients were treated with CVVH for a total of 113 days. Median treatment time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile) versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial blood pressures (MAPs) did not differ significantly for patients treated with EDD when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P = 0.078), midway through daily treatment (70 versus 68 mm Hg for CVVH; P = 0.083), or at the end of treatment (71 versus 69 mm Hg for CVVH; P = 0.07). Net daily ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000 mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P = 0.514). Anticoagulation requirements were significantly less for patients treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus 21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P < 0.001). We found that EDD eliminated the need for constant supervision of the dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage more than one treatment. Overall, EDD was well tolerated by the majority of patients, offered many of the same benefits provided by CVVH, and was technically easier to perform.

Aminoethylprolyl peptide nucleic acids (aepPNA): chiral PNA analogues that form highly stable DNA:aepPNA2 triplexes.

[formula: see text] The replacement of the glycyl component in the peptide nucleic acid (PNA) backbone by a prolyl unit bearing a nucleobase leads to the aminoethylprolyl (aep) PNAs, which are chiral and cationic. The homooligomeric aepPNA binds to complementary DNA sequences with high affinity and sequence specificity, forming highly stable triplexes.

Extended daily dialysis vs. continuous hemodialysis for ICU patients with acute renal failure: a two-year single center report.

Extended daily dialysis (EDD) is an easily implemented alternative to continuous renal replacement therapy (CRRT) in the intensive care unit (ICU). Since EDD offers most of the advantages of CRRT, we sought to compare the effectiveness of these two modalities. In this 2-year study, 54 ICU patients with ARF were treated with either continuous hemodialysis (CHD) or EDD. Oliguria was present in 64% of patients who received CHD vs. 73% of EDD patients (p=NS) while 93% of CHD and 81% of EDD patients required mechanical ventilation (p=NS). Patients treated with EDD were younger than those who received CHD (47.0 +/- 12.6 vs. 56.7 +/- 13.7, p=0.009), but there were no significant differences in gender or mean APACHE II scores at the time of randomization. Mean arterial blood pressures measured during treatment were maintained between 70 and 80 mmHg for both EDD and CHD and average daily serum electrolyte levels fell within normal ranges for EDD and CHD. Average daily fluid input and output were 5.8 +/- 3.3 L and 6.0 +/- 3.2 L for CHD vs. 3.3 +/- 2.6 and 3.0 +/- 1.7 L for EDD after exclusion of data from 2 burn patients. Hourly heparin anticoagulation rates were 1080 U/hour for CHD and 643 U/hour for EDD, p=0.02. Anticoagulation-free treatments were performed during 43% of all EDD treatments vs. 21% of all CHD treatments, p<0.001. Clotting of the dialyzer or circuit occurred at least once during 51% of all CHD treatment days vs. 22% of EDD treatments (p<0.001). We conclude that EDD is a safe, effective alternative to CRRT that offers comparable hemodynamic stability and excellent small solute control.

Synthesis and evaluation of prolyl carbamate nucleic acids (PrCNA).

Carbamate linked prolyl nucleic acids are obtained in high yield and purity under mild conditions in solution and solid phase. p-Nitrophenylchloroformate is used as the activating reagent for alcohol. Homooligomers of PrCNA do not bind to DNA. The introduction of this modification in PNA sequences destabilizes the triplexes, inspite of enhancement in the base stacking.

Engineering preferences of hairpin PNA binding to complementary DNA: effect of N7G in aeg/aep PNA backbone.

AegPNA and aepPNA monomeric units bearing the N7-guanine nucleobase as a substitute for C+ have been demonstrated to bind to a GC base-pair of a duplex in a pH-independent manner when placed in the third strand. The aepPNA backbone exerts a preference for binding in the antiparallel Hoogsteen mode over the parallel Hoogsteen mode.

Constrained flexibility in PNA: DNA binding studies with bridged aminopropylglycyl PNA.

Introduction of methylene bridges in aegPNA and apgPNA molecules give rise to cyclic five and six membered ring structures. Synthesis of a new six membered cyclic PNA monomer, aminopipecolyl PNA (pipPNA) is reported. Incorporation of pipPNA into PNA oligomers and comparative binding with target DNA sequences is studied.

CT imaging features of obturator prostheses in patients following palatectomy or maxillectomy.

Palatal tumors are often treated with palatectomy or maxillectomy. The resulting surgical defect produces an oroantral communication. An obturator is a removable prosthesis used to close the palatal or maxillectomy defect. Fifteen patients who had undergone palatectomy or maxillectomy for carcinoma and subsequent obturator prosthesis placement were retrospectively studied. Obturators were characterized by Hounsfield units and were subdivided into 3 CT imaging groups: either hyperattenuated, hollow (air-containing), or heterogeneous (isoattenuated to hyperattenuated with internal foci of air). Eight patients had hyperattenuated obturators either representing acrylic resin or Trusoft. Four patients had hollow obturators also composed of acrylic resin or Trusoft. Three patients had heterogeneous obturators, which were composed of only Trusoft. The postoperative imaging of patients treated for palatal or maxillary tumors can be complicated by the presence of obturator prostheses. The intent of this article was to familiarize the reader with the CT imaging features of obturator prostheses.