THERAPEUTIC OPTION FOR CHILDREN WITH ESOPHAGEAL CAUSTIC STENOSIS

Caustic ingestion is a leading cause of esophageal stenosis in children. Herein we report four cases using mitomycin C (MMC), a drug that inhibits cell division, protein synthesis and fibroblast proliferation and has been used as an adjuvant therapy for caustic esophageal stenosis that is recalcitrant to conventional dilation techniques. A retrospective chart review was performed on four pediatric patients with severe, recurrent esophageal stricture after caustic ingestion. The patients had required six to 20 esophageal dilations over a 4–16‐month period before MMC application. MMC was applied after an endoscopic dilation on saturated pledgets at a dose of 0.1 mg/mL for 2 min in the area where the strictures had been lyzed. From the four children treated with MMC, two have been asymptomatic for 16 and 20 months and two still require esophageal dilation, however, at longer intervals. All patients have shown satisfactory weight gain with food intake exclusively per oral. Although further studies are required, there is strong evidence that MMC is a safe and effective adjuvant therapy in the treatment of esophageal caustic stenosis.     

Matched cohort study of topical tranexamic acid in cementless primary total hip replacement

Purpose

Tranexamic acid has been shown to be effective in reducing blood loss after total hip replacement. The purpose of this study was to prospectively assess the effectiveness of topical TXA use to reduce blood loss after primary total hip replacement and to compare these outcomes with those of a matched control group from a similar cohort that did not have received tranexamic acid.

Methods

This is a prospective matched control study to assess the effect of a 2 g topical tranexamic acid in 50 mL physiological saline solution in total hip replacement. Primary outcomes were hemoglobin and hematocrit drop, and total blood loss. Secondary outcomes were transfusion rates, length of hospital stay, deep vein thrombosis, and pulmonary embolism events.

Results

We could match 100 patients to a control group. There were no statistical significantly differences between the two groups. The hemoglobin and hematocrit postoperative values were significantly higher in topical tranexamic acid group than in control group (P?<?0.001). The mean total blood loss was 769 in topical tranexamic acid group and 1163 in control group with significant differences (P?=?0.001), which meant 34% reduction in total blood loss. Length of stay was lower in topical tranexamic acid group. The risk of deep vein thrombosis and pulmonary events did not increase.

Conclusions

A single dose of 2 g tranexamic acid in 50 mL physiological saline solution topical administration was effective and safe in reducing bleeding in patients undergoing unilateral primary non-cemented total hip replacement compared to a matched control group.

     

Cognitive rehabilitation combined with drug treatment in Alzheimer's disease patients: a pilot study

OBJECTIVE: To study the efficacy of cognitive rehabilitation combined with acetylcholinesterase inhibitor (AChE-I) treatment in patients with mild Alzheimer's disease and their relatives. METHOD: Thirteen patients with mild Alzheimer's disease treated with rivastigmine 6-12 mg/day for more than two months started cognitive rehabilitation training. Before and after the cognitive rehabilitation training patients were assessed through cognitive tests, activities of daily living scale, neuropsychological battery and scales to evaluate caregivers' depressive and anxiety symptoms. Six patients were randomized to a combined treatment group (AChE-I plus cognitive rehabilitation and caregiver support) and seven patients to a control group (AChE-I only) and followed up for five months. RESULTS: Mini-Mental State Examination (MMSE) scores (p = 0.047) and backward digit span scores (p = 0.018) were significantly different between the groups on follow-up. The combined treatment group showed a better positive treatment effect on cognitive and neuropsychological tests applied to patients and reduction of psychiatric symptoms was observed in their caregivers (nonsignificant). CONCLUSION: Cognitive rehabilitation associated with AChE-I treatment can potentially be useful to stabilize or improve cognitive and functional performance of patients with mild Alzheimer's disease and can reduce caregivers' psychiatric symptoms.     

Activity of posaconazole in the treatment of central nervous system fungal infections

OBJECTIVES: A multinational, multicentre, open-label clinical trial was conducted to evaluate the safety and efficacy of posaconazole, an extended-spectrum triazole antifungal agent, in subjects with invasive fungal infections who had refractory disease or who were intolerant of standard antifungal therapy. In this subanalysis, we report on those subjects in this trial who had a fungal infection that involved the CNS. METHODS: Subjects received posaconazole oral suspension 800 mg/day in divided doses for up to 1 year; however, subjects could receive additional therapy as part of a treatment-use extension protocol. A blinded, third-party data review committee determined subject eligibility and outcome. RESULTS: Of the 330 subjects who enrolled in the study, 53 had infections of the CNS, of which 39 were considered evaluable for efficacy. Most had refractory disease (37 of 39) and underlying HIV infection (29 of 39). Twenty-nine subjects had cryptococcal infections, and 10 had infections caused by other fungal pathogens [Aspergillus spp. (four), Pseudallescheria boydii (two), Coccidioides immitis (one), Histoplasma capsulatum (one), Ramichloridium mackenziei (one), and Apophysomyces elegans plus a Basidiomycetes sp. (one)]. Successful outcomes were observed in 14 of 29 (48%) subjects with cryptococcal meningitis and five of 10 (50%) subjects with CNS infections due to other fungal pathogens. Posaconazole was well tolerated. CONCLUSIONS: These data suggest that posaconazole, as an oral medication, has clinical activity against fungal infections of the CNS and may provide a valuable alternative to parenteral therapy in patients failing existing antifungal agents.     

Utilization of multiple SAVI SCOUT surgical guidance system reflectors in the same breast: A single‐institution feasibility study

SAVI SCOUT Surgical Guidance System has been shown to be a reliable and safe alternative to wire localization in breast surgery. This study evaluated the feasibility of using multiple reflectors in the same breast. We performed an IRB‐approved, HIPAA‐compliant, single‐institution retrospective review of 183 patients who underwent breast lesion localization and excision using SAVI SCOUT Surgical Guidance System (Cianna Medical) between June 2015 and January 2017. We performed a subset analysis in 42 patients in whom more than one reflector was placed. Specimen radiography, pathology, distance between reflectors, target removal, margin positivity, and complications were evaluated. Among 183 patients, 42 patients had more than one reflector placed in the same breast to localize 68 lesions. Benign (n = 6, 8.8%), high‐risk (n = 23, 33.8%), and malignant (n = 39, 57.4%) lesions were included. Thirty‐six patients (85.7%) had a total of 2 reflectors placed and 6 patients had a total of 3 reflectors placed (14.3%). The indications for multiple reflector placement in the same breast included multiple separate lesions (n = 23) and bracketing of large lesions (n = 19). The mean distance between the reflectors was 42 mm (22‐93 mm). All lesions were successfully targeted and retrieved. Of 39 malignant lesions, 10.3% (n = 4) had positive margins and 10.3% (n = 4) had close (<1 mm) margins at surgery. All patients with positive margins underwent re‐excision. No complications occurred preoperatively, intra‐operatively, or postoperatively. The use of multiple SAVI SCOUT reflectors for localizing multiple lesions in the same breast or bracketing large lesions is feasible and safe.     

Chronic Granulomatous Disease-Like Presentation of a Child with Autosomal Recessive PKCδ Deficiency

Journal of Clinical Immunology - Autosomal recessive (AR) PKCδ deficiency is a rare inborn error of immunity (IEI) characterized by autoimmunity and susceptibility to bacterial, fungal, and...     

Multiple-dose pharmacokinetics of imipenem-cilastatin.

We characterized the pharmacokinetic profile of imipenem-cilastatin administered intravenously to six normal volunteers in a dose of 1,000 mg of each drug every 6 h for 40 doses. The plasma concentrations of imipenem and cilastatin 1 h after the end of a 30-min infusion were 18.7 (+/- 2.1) and 19.1 (+/- 4.6), 20.0 (+/- 3.2) and 17.8 (+/- 4.8), and 23.4 (+/- 2.3) and 19.1 (+/- 3.5) micrograms/ml in the 1st, 17th, and 37th dosing intervals, respectively. The central compartment volumes of distribution for imipenem and cilastatin were 0.16 (+/- 0.05) and 0.14 (+/- 0.03) liter/kg, respectively. Elimination half-lives were short: 0.93 (+/- 0.09) h for imipenem and 0.84 (+/- 0.11) h for cilastatin. Plasma clearances were 12.1 (+/- 0.06) liters/h per 1.73 m2 for imipenem and 12.4 (+/- 1.1) liters/h per 1.73 m2 for cilastatin. Renal clearance accounted for 54% of the plasma clearance of imipenem and 69% of the plasma clearance of cilastatin. The concentrations of imipenem in plasma and urine remained above the MICs of the vast majority of pathogens throughout the dosing interval.     

Bias and error in estimates of equilibrium free-energy differences from nonequilibrium measurements

In 1997, Jarzynski proved a remarkable equality that allows one to compute the equilibrium free-energy difference DeltaF between two states from the probability distribution of the nonequilibrium work W done on the system to switch between the states, e-DeltaF/kappaT =e-W/kappaT [Jarzynski, C. (1997) Phys. Rev. Lett. 87, 2690-2693]. The Jarzynski equality provides a powerful free-energy difference estimator from a set of N irreversible experiments and is closely related to free-energy perturbation, a common computational technique for estimating free-energy differences. Despite the many applications of the Jarzynski estimator, its behavior is only poorly understood. In this article we derive the large N limit for the Jarzynski estimator bias, variance, and mean square error that is correct for arbitrary perturbations. We then analyze the properties of the Jarzynski estimator for all N when the probability distribution of work values is Gaussian, as occurs, for example, in the near-equilibrium regime. This allows us to quantitatively compare it to two other free-energy difference estimators: the mean work estimator and the fluctuation-dissipation theorem estimator. We show that, for near-equilibrium switching, the Jarzynski estimator is always superior to the mean work estimator and is even superior to the fluctuation-dissipation estimator for small N. The Jarzynski-estimator bias is shown to be the dominant source of error in many cases. Our expression for the bias is used to develop a bias-corrected Jarzynski free-energy difference estimator in the near-equilibrium regime.