Management of Cartilage Conduction Hearing Aids in Pediatric Patients.

Forty-nine children who started wearing cartilage conduction hearing aids (CC-HAs) before completing elementary school (17 with bilateral hearing loss and 32 with unilateral hearing loss) were followed-up and examined. The wearing and utilization status of the CC-HA and its progress to date were evaluated. In addition, 33 participants who purchased the CC-HAs were interviewed to assess the wearing effect. Eleven of seventeen children with bilateral hearing loss and 25 of 32 children with unilateral hearing loss continued to use the CC-HAs. In terms of wearing effect, a good wearing effect was reported, even by those with unilateral hearing loss. In cases where it was difficult to wear CC-HAs stably with pasting or ear tips, it was possible to fix them stably using commercially available hair bands and eyeglass vines. In two cases, the CC-HAs were worn from infancy. With ingenuity and appropriate educational and medical support, it is possible to wear CC-HAs from infancy.

High Plasma tPAPAI-1C Levels May Be Related to a Poor Prognosis in Patients with Severe or Critical COVID-19: A Single-Center Retrospective Study.

Severe novel coronavirus disease 2019 (COVID-19) patients have a high incidence of thrombotic complications and mortality. The pathophysiology of coagulopathy involves fibrinolytic system impairment and vascular endothelial damage. This study examined coagulation and fibrinolytic markers as outcome predictors. In an observational study of 164 COVID-19 patients admitted to our emergency intensive care unit, hematological parameters on days 1, 3, 5, and 7 were retrospectively compared between survivors and nonsurvivors. Nonsurvivors had a higher APACHE II score, SOFA score, and age than survivors. Nonsurvivors also had a significantly lower platelet count and significantly higher plasmin/α2plasmin inhibitor complex (PIC), tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPAPAI-1C), D-dimer, and fibrin/fibrinogen degradation product (FDP) levels than survivors throughout the measurement period. The 7-day maximum or minimum values of the tPAPAI-1C, FDP, and D-dimer levels were significantly higher in nonsurvivors. A multivariate logistic regression analysis showed that the maximum tPAPAI-1C (OR = 1.034; 95% CI,1.014-1.061; p = 0.0041) was an independent factor affecting mortality, with an area under the curve (AUC) of 0.713 (optimum cut-off of 51 ng/mL; sensitivity, 69.2%; and specificity, 68.4%). COVID-19 patients with poor outcomes exhibit exacerbated coagulopathy with fibrinolysis inhibition and endothelial damage. Consequently, plasma tPAPAI-1C might be a useful predictor of the prognosis in patients with severe or critical COVID-19.

Prognostic Factors Associated With Mortality of Patients With COVID-19 Requiring Ventilator Management: A Retrospective Cohort Study.

Aim There are few reports on the prognostic factors associated with mortality in coronavirus disease (COVID-19) patients with critical disease. This study assessed prognostic factors associated with mortality of patients with critical COVID-19 who required ventilator management. Methods This single-center, retrospective cohort study used medical record data of COVID-19 patients admitted to an emergency ICU at a hospital in Japan between March 1, 2020 and September 30, 2021, and provided with ventilator management. Multivariable logistic regression was used to identify factors associated with mortality. Results Seventy patients were included, of whom 29 (41.4%) died. The patients who died were significantly older (median: 69 years) (interquartile range [IQR]: 47-82 years) than the patients who survived (62 years [38-84 years], p<0.007). In addition, patients who died were significantly less likely to have received steroid therapy than patients who survived (25 [86.2%] vs. 41 [100%], p=0.026). In the multivariable analysis, age was identified as a significant prognostic factor for mortality and the risk of death increased by 6% for every one-year increase in age (OR: 1.06; 95% CI: 1.00-1.13; p=0.048). Medical history was not a risk factor for death. Conclusion Age was a predictor of mortality in critically ill patients with COVID-19. Therefore, the indications for critical care in older patients with COVID-19 should be carefully considered.

Protocol for laparoscopic cholecystectomy: Is it rocket science?

Laparoscopic cholecystectomy (LC) does not require advanced techniques, and its performance has therefore rapidly spread worldwide. However, the rate of biliary injuries has not decreased. The concept of the critical view of safety (CVS) was first documented two decades ago. Unexpected injuries are principally due to misidentification of human factors. The surgeon's assumption is a major cause of misidentification, and a high level of experience alone is not sufficient for successful LC. We herein describe tips and pitfalls of LC in detail and discuss various technical considerations. Finally, based on a review of important papers and our own experience, we summarize the following mandatory protocol for safe LC: (1) consideration that a high level of experience alone is not enough; (2) recognition of the plateau involving the common hepatic duct and hepatic hilum; (3) blunt dissection until CVS exposure; (4) Calot's triangle clearance in the overhead view; (5) Calot's triangle clearance in the view from underneath; (6) dissection of the posterior right side of Calot's triangle; (7) removal of the gallbladder body; and (8) positive CVS exposure. We believe that adherence to this protocol will ensure successful and beneficial LC worldwide, even in patients with inflammatory changes and rare anatomies.

Significance of proximal tubular metabolism of advanced glycation end products in kidney diseases.

Advanced glycation end products (AGEs) are formed by the nonenzymatic Maillard reaction between sugars and proteins. Low-molecular weight AGEs are filtered by renal glomeruli and then reabsorbed and metabolized by proximal tubule cells (PTCs). High-molecular weight AGEs are also delivered to PTCs in proteinuric states. In patients with diabetes, AGE generation is increased, and the actions of AGEs on PTCs are likely involved in the pathogenesis of diabetic nephropathy. In patients with chronic renal failure (CRF), reduced renal metabolism of AGEs likely accounts for the accumulation of AGEs in serum, leading to uremic complications including dialysis-related amyloidosis. AGE precursors such as reactive carbonyl compounds also accumulate in the sera of patients with CRF. It is likely that PTCs take up AGEs and AGE precursors via specific endocytotic receptors or transporters. Megalin is a multiligand endocytotic receptor that is abundantly expressed on PTCs. There is evidence that megalin is involved in the cellular uptake and degradation of AGEs. We previously reported a cell therapy model involving implantation of megalin-expressing cells into experimental mice with renal failure for elimination of uremic toxin proteins. Further studies are needed to clarify the molecular mechanisms of the metabolism of AGEs and their precursors to develop a strategy for the treatment of diabetic nephropathy and uremic complications of CRF.

Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules.

Liver-type fatty acid binding protein (L-FABP) binds with high affinity to hydrophobic molecules including free fatty acid, bile acid and bilirubin, which are potentially nephrotoxic, and is involved in their metabolism mainly in hepatocytes. L-FABP is released into the circulation, and patients with liver damage have an elevated plasma L-FABP level. L-FABP is also present in renal tubules; however, the precise localization of L-FABP and its potential role in the renal tubules are not known. In this study, we examined the cellular and subcellular localization of L-FABP in the rat kidney and tried to determine from where the L-FABP in kidney tissues had originated. Immunohistochemical studies of kidney sections localized L-FABP in the lysosomes of proximal tubule cells (PTC). In rats with carbon tetrachloride (CCl4)-induced acute liver injury, we detected high levels of L-FABP in the circulation and in the kidney compared with those in the control rat by immunoblotting, while reverse transcription-polymerase chain reaction showed that the level of L-FABP mRNA expression in the kidney of CCl4-treated rats was low and did not differ from that in the control rat. When 35S-L-FABP was intravenously administered to rats, the kidneys took up 35S-L-FABP more preferentially than the liver and heart, and histoautoradiography of kidney sections revealed that 35S-L-FABP was internalized via the apical domains of PTC. Quartz-crystal microbalance analysis revealed that L-FABP bound to megalin, a multiligand endocytotic receptor on PTC, in a Ca2+-dependent manner. Degradation assays using megalin-expressing rat yolk sac tumor-derived L2 cells demonstrated that megalin mediated the cellular uptake and catabolism of 125I-L-FABP. In conclusion, circulatory L-FABP was found to be filtered by glomeruli and internalized by PTC probably via megalin-mediated endocytosis. These results suggest a novel renal uptake pathway for L-FABP, a carrier of hydrophobic molecules, some of which may exert nephrotoxic effects.

Evidence indicating that renal tubular metabolism of leptin is mediated by megalin but not by the leptin receptors.

Leptin is secreted by adipocytes and is a circulating factor that regulates food intake and energy expenditure. Its serum level is elevated in patients with renal failure and has been suggested to be associated with malnutritional factors in these patients. Leptin has been suggested to be primarily metabolized by the kidneys, although the precise molecular mechanisms are not known. The purpose of this study was to determine the nephron segments and potential receptors involved in renal leptin metabolism. To determine the segment involved in leptin uptake, we performed histoautoradiography of kidney sections obtained from rats that had been injected iv with (125)I-leptin. The ability of megalin, a multiligand endocytic receptor in the proximal tubules, to bind and endocytose leptin was examined by ligand blotting analysis, quartz-crystal microbalance, and degradation assays using megalin-expressing rat yolk sac L2 cells. Immunohistochemistry was performed to localize leptin receptors (LEP-R) in the rat kidney using two antibodies that recognize different epitopes on the LEP-R proteins. Circulating (125)I-leptin was filtered by glomeruli and internalized by proximal convoluted tubules. Megalin bound leptin in the presence of Ca(2+) and mediated its cellular internalization and degradation. On immunohistochemistry, LEP-R were localized in the proximal straight tubules, loops of Henle, distal tubules, and collecting ducts. In conclusion, circulating leptin was filtered by glomeruli and taken up by proximal convoluted tubules, where megalin likely mediates its binding and uptake. The localization of LEP-R suggests that they are not primarily involved in leptin metabolism in the proximal tubules.

Hypersensitivity to paraoxybenzoic Acid esters (parabens) in a dialysis patient.

A 24-year-old woman undergoing chronic dialysis therapy who had been diagnosed as having 'heparin allergy' presented acute allergic reaction after the intracatheter injection of a heparin agent. Further investigation revealed that mild eosinophilia had persisted for more than 3 years before this incidence despite avoiding the use of heparin agents. The leukocyte migration inhibition test (LMIT) showed that heparin agent A which was used for the patient showed positive reaction while heparin agent B which was not used for the patient showed a negative reaction. Paraoxybenzoic acid esters (parabens) are contained in heparin agent A but not in heparin agent B. Parabens showed positive reactions on LMIT. Parabens are the most common preservatives in drugs, foods, and cosmetics and they sometimes induce allergic reactions through percutaneous and possibly ingestive sensitization. However, they cause more severe allergic reactions when used intravenously. We concluded that the allergen in this patient was not heparin but parabens. Hypereosinophilia of unknown origin often occurs in dialysis patients. Such patients may be hypersensitive to parabens.