Early nephrectomy in neonates with symptomatic autosomal recessive polycystic kidney disease

IntroductionAutosomal recessive polycystic kidney disease (ARPKD) is a rare cause of renal failure with a highly variable clinical course. Patients who are symptomatic early in life frequently require early nephrectomy and peritoneal dialysis. In these patients there are little data to guide clinicians on whether to select unilateral nephrectomy or bilateral nephrectomy at the initial operative intervention. We review our experience with this disease process.MethodsA retrospective review was performed of 11 patients at our institution with ARPKD symptomatic within the first month of life. Charts were reviewed for relevant clinical data, and patients were divided into groups based on undergoing either unilateral or bilateral nephrectomy at their initial intervention. The decision for unilateral versus bilateral nephrectomy was decided by the clinical team without any available guidelines.ResultsOf the 11 patients reviewed, two patients died within the first two weeks from other complications. The remaining 9 all required nephrectomy, with 5 undergoing synchronous bilateral nephrectomy, and 4 undergoing initial unilateral nephrectomy. All four patients required removal of their contralateral kidney, a median of 25.5 days later. There was no difference in mortality, ventilator free days, or time to full feeds between the two groups, although the group undergoing initial unilateral nephrectomy had more TPN days than their counterparts (28 vs 17 days, p = 0.014).ConclusionsIn our cohort, there were few significant differences between the groups based on choice of initial unilateral or bilateral nephrectomy, and all children ultimately required removal of both kidneys. These data suggest that anesthetic exposures and other clinical outcomes might be optimized by initial bilateral nephrectomy.Level of evidenceIII.     

Transcriptomic and Immunophenotypic Characterization of Tumor Immune Microenvironment in Squamous Cell Carcinoma of the Oral Tongue

The tumor immune microenvironment of oral tongue squamous cell carcinoma may be accountable for differences in clinical behavior, particularly between different age groups. We performed RNA expression profiling and evaluated tumor infiltrating lymphocytes (TILs) and their T-cell subsets in order to assess the functional status of oral tongue squamous cell carcinoma tumor microenvironment and detect potentially clinically useful associations. Archival surgical pathology material from sixteen oral tongue squamous cell carcinoma patients was microscopically evaluated for TIL densities. RNA was extracted from macrodissected whole tumor sections and normal controls and RNA expression profiling was performed by the NanoString PanCancer IO 360 Gene Expression Panel. Immunostains for CD4, CD8 and FOXP3 were evaluated manually and by digital image analysis. Oral tongue squamous cell carcinomas had increased TIL densities, numerically dominated by CD4 + T cells, followed by CD8 + and FOXP3 + T cells. RNA expression profiling of tumors versus normal controls showed tumor signature upregulation in inhibitory immune signaling (CTLA4, TIGIT and PD-L2), followed by inhibitory tumor mechanisms (IDO1, TGF-β, B7-H3 and PD-L1). Patients older than 44 years showed a tumor microenvironment with increased Tregs and CTLA4 expression. Immunohistochemically assessed CD8% correlated well with molecular signatures related to CD8 + cytotoxic T-cell functions. FOXP3% correlated significantly with CTLA4 upregulation. CTLA4 molecular signature could be predicted by FOXP3% assessed by immunohistochemistry (R² = 0.619, p = 0.026). Oral tongue squamous cell carcinoma hosts a complex inhibitory immune microenvironment, partially reflected in immunohistochemically quantified CD8 + and FOXP3 + T-cell subsets. Immunohistochemistry can be a useful screening tool for detecting tumors with upregulated expression of the targetable molecule CTLA4.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01229-w) contains supplementary material, which is available to authorized users.     

Therapeutic Drug Monitoring in the Elderly

Therapeutic drug monitoring (TDM) is defined as the strategy by which the dosing regimen for a patient is guided by repealed measurements of plasma drug concentrations. TDM is also used to confirm drug poisoning and toxicity, to diagnose adverse drug reactions, and to verify patient compliance with drug regimens. There is a scarcity of data about the use of TDM in treating the elderly, but general inferences can be made based on pharmacokinetic and pharmacodynamic studies in older populations and on investigations in younger individuals. Despite its important limitations TDM seems to be an important tool in drug therapy management in the elderly given the increased frequency of chronic medical conditions, polypharmacy, drug interactions, and the atypical presentation of adverse drug reactions in this population.     

Comparison of left ventricular performance in healthy young women and men during exercise

Background

Previous studies show sex-related differences in left ventricular (LV) response to exercise. It is not clear, however, whether these differences are also seen in younger healthy subjects.

Methods and Results

This study examined the changes in LV performance during dynamic upright exercise in 11 healthy men and 19 healthy young women according to the Bruce protocol and an individualized ramp protocol. There were no significant differences between the two protocols for either men or women in heart rate, blood pressure, LV ejection fraction (EF) (measured by ambulatory nuclear detector), and measured oxygen consumption. The peak oxygen consumption was higher in men than in women (44±13 vs 36±9 ml/kg/min; p<0.05), but the peak heart rate, systolic blood pressure, and EF were similar. The change in EF (from rest to exercise) was 19%±8% in men and 19%±11% in women with the Bruce protocol (difference not significant) and 26%±9% in men and 19%±6% in women with the ramp protocol (difference not significant). At peak exercise, both men and women showed an increase in end-diastolic volume (29%±14% vs 23%±11%; difference not significant) and a decrease in end-systolic volume (41%±15% vs 43%±21%) (difference not significant). The increase in cardiac output during exercise was due to an increase in heart rate and stroke volume in both men and women. At submaximal exercise, however, the decrease in end-systolic volume was less in women than in men (p<0.05).

Conclusions

There are no sex-related differences in compensatory mechanism during dynamic execise in healthy subjects. The changes in contractility and LV volume are not affected by the exercise protocol.     

Fluoride bioactive glass paste improves bond durability and remineralizes tooth structure prior to adhesive restoration

ObjectiveThe current study aimed at examining a fluoride containing bioactive glass (BiominF®) paste as a temporary filling material capable of remineralizing the demineralized enamel or dentin, and its ability to decrease a simulated dentinal fluids pressure on the resin/dentin interface, without affecting the shear bond strength of a universal bonding agent to enamel and dentin.Methods60 premolars were utilized for the acid resistance, trans-microradiography (TMR) and shear bond strength (SBS) experiments. Enamel and dentin discs were demineralized for 4 days to create a subsurface demineralized zone followed by applying BiominF® paste, 1.23% acidulated phosphate fluoride, or a temporary filling material for 24 h.30 extracted human non-carious third molars were utilized for the pulpal pressure experiment in which direct communication to the pulp chamber was created by cutting at a level approximately 1 mm below the cemento-enamel junction while the coronal enamel was ground to expose mid coronal dentin. The dentin surface was exposed to a simulated pulpal pressure. The dentin surfaces had BiominF® paste, an oxalate desensitizing agent, or temporary filling material followed by application of a universal adhesive system.ResultsOne way ANOVA showed that BiominF® paste remineralized effectively the demineralized enamel or dentin, did not affect the bond strength of the enamel and dentin surfaces to the tested adhesive system p < 0.05, and improved the acid resistance of the demineralized enamel and dentin against a secondary erosive challenge. Moreover, BiominF® paste decreased the nanoleakage expression in the dentin/adhesive interface exposed to a simulated pulpal pressure.SignificanceBiominF® paste may serve as a temporary filling material that may improve the longevity of adhesive restorations and help to conserve tooth structures by preserving the demineralized enamel and dentin form cutting during cavity preparation.