Tracheal Stenosis after Tracheostomy

INTRODUCTIONTracheal stenosis is a late and usually non-life threatening complication of surgical and percutaneous tracheostomies (PDT) as well as delayed endotracheal extubation.METHODSWe undertook a retrospective review of all patients who underwent a surgical tracheostomy over a 10 year period. Patients were included in the study if they had CT or MRI imaging of the tracheostomy site both pre-operatively and six or more weeks post operatively. Patients whose imaging was not available were excluded (n = 3) as were those patients who still had a tracheostomy in situ (n = 8). In total 91 patients were included in the study. In the same period 1170 surgical tracheostomies were performed by the maxillofacial surgeons. The images were analysed by a radiologist and the degree of stenosis reported.RESULTSAll 91 patients underwent a tracheostomy with a window. 83 patients did not demonstrate any stenosis. Looking at the remaining 8 patients with stenosis: 6 patients had stenosis of less than 25%, 1 patient had stenosis between 25-50% and 1 patient had stenosis greater than 50%. Both patients with stenosis greater than 25% had more than one surgical tracheostomy.CONCULSIONWe have shown that the risk of stenosis is 8.8%, lower than often quoted in literature, and when it occurs it is likely to be symptomatic only in severe stenosis. Our main risk of stenosis was repeat surgical tracheostomies which also seems to be linked to a greater degree of stenosis.     

Clinical outcome of living donor kidney transplantation across simultaneous ABO and HLA incompatibility: Single center experience of first ten cases

Background and aimsPreconditioning using different protocols has been tested to prevent antibody mediated rejection (ABMR) individually for ABO and HLA incompatibility. However, simultaneous presence of both barriers is still less explored. The aim of this study was to report outcomes of institutional desensitization protocol in renal transplant recipients with simultaneous ABO and HLA incompatibility.Materials and methodsThis was a retrospective study conducted from October 2015 to December 2018. All patients with a clinical diagnosis of dialysis dependent chronic kidney disease (CKD), who were prospective coexistent HLA and ABO incompatible renal transplant recipients were included in the study. Patients were followed up and graft function and patient survival was assessed at 1 y from the date of transplant.ResultsMedian and mode baseline anti-A titers were 64, while median and mode baseline anti-B titers were 256. All recipients were discharged by tenth postoperative day. None of the patients had any bleeding complications. Post transplant infection rate was found to be 20 %. A total of 54 therapeutic plasma exchange (TPE) procedures were performed before transplant and 8 were performed after transplant. Graft survival and patient survival was 100 % at 3, 6, 9, and 12 months. Range and mean follow-up period was 15–42 months and 23 months respectively. Mean glomerular filtration rate (GFR) at 1 y using the CKD-EPI equation was 85.25 ± 13.76 mL/min. Biopsy proven ABMR was observed in one case only which was managed with TPE and immunosuppression.ConclusionSimultaneous ABO and HLA incompatibility in renal transplant recipients can be managed successfully with adequate preconditioning and careful monitoring.     

Clinical utility of EUS-guided fine-needle aspiration of mediastinal masses in the absence of known pulmonary malignancy

BACKGROUND: Mediastinal masses represent a diagnostic challenge because of their proximity to numerous critical structures, difficulty of access for tissue sampling, and myriad potential pathologic etiologies. A large, single-center experience with EUS-guided fine-needle aspiration (EUS-FNA) in the diagnosis of non-lung cancer-related mediastinal masses is presented. METHODS: An EUS database was reviewed and all cases of mediastinal mass or lymphadenopathy encountered between 1994 and 1999 were included. Final diagnoses were determined by EUS-FNA cytology and clinical follow-up. RESULTS: Forty-nine patients were identified (27 women, 22 men; mean age 58.1 years, range 30-89 years). A malignant process was diagnosed in 22 cases (45%) and a benign process in 24 (49%). The EUS-FNA specimen was nondiagnostic in 3 cases (6%). An accurate diagnosis was made in 46 of the 49 patients (94%). No complication was noted. CONCLUSIONS: EUS-FNA is a minimally invasive technique that facilitates detection and tissue sampling of mediastinal masses. It is a safe procedure that can be performed with the patient under conscious sedation in an outpatient setting.     

The effect of tranexamic acid on artificial joint materials: a biomechanical study (the bioTRANX study)

Background

Tranexamic acid (TXA) has been successfully used to reduce bleeding in joint replacement. Recently local TXA has been advocated to reduce blood loss in total knee or hip replacement; however, this raised concerns about potential adverse effects of TXA upon the artificial joint replacement.

Materials and methods

In this biomechanical study we compared the effects of TXA and saline upon the following biomechanical properties of artificial joint materials—(1) tensile properties (ultimate strength, stiffness and Young’s modulus), (2) the wear rate using a multi-directional pin-on-plate machine, and (3) the surface topography of pins and plates before and after wear rate testing.

Results

There were no significant differences in tensile strength, wear rates or surface topography of either ultra-high-molecular-weight polyethylene pins or cobalt chromium molybdenum metal plates between specimens soaked in TXA and specimens soaked in saline.

Conclusion

Biomechanical testing shows that there are no biomechanical adverse affects on the properties of common artificial joint materials from using topical TXA.

Level of evidence

V     

Increase in minimum inhibitory concentration to quinolones and ceftriaxone in salmonellae causing enteric fever

Multidrug resistance among Salmonella typhi is well known. Reports of treatment failure in enteric fever with Ciprofloxacin made us undertake this study to determine the antibiotic susceptibility pattern of S. typhi and S. paratyphi A isolated from typhoid bacteremia cases, by disc diffusion and MIC by broth dilution method. A total of 50 strains were tested, 48 of Salmonella typhi and 2 of S. paratyphi A. The disc diffusion method was done using ampicillin, chloramphenicol, cotrimoxazole, tetracycline, ciprofloxacin, ofloxacin, cefuroxime and ceftriaxone as antibiotics. The MIC was performed using ciproloxacin, ofloxacin and ceftriaxone based on standard procedure. ACCOT resistance as determined by disc diffusion method was seen in 68% of isolates. All the strains remained susceptible to flouroquinolones cephalosporins and aminoglycosides. The MIC of ciprofloxacin, ofloxacin and ceftriaxone were in the recommended range of susceptibility as given by NCCLS, 14 (28%) strains had MIC of ciprofloxacin greater than 0.5 ug/ml with 4 strains having an MIC of 1.56 ug/ml; 25 (50%) strains had MIC of ofloxacin greater than 0.5 ug/ml and 20 (40%) strains had MIC of ceftriaxone greater than 0.5 ug/ml. The high levels of MIC of ciprofloxacin may account for treatment failure cases. The rising levels of MIC of ofloxacin and ceftriaxone in S. typhi and S. paratyphi is also of concern. We document here the emergence of high levels of MIC not only to ciprofloxacin, but also ofloxacin and ceftriaxone in S. typhi and S. paratyphi A. We recommend that MIC levels of ofloxacin and ceftriaxone should be monitored along with ciprofloxacin in treatment failure cases of enteric fever.     

Parkin cooperates with GDNF/RET signaling to prevent dopaminergic neuron degeneration

Parkin and the glial cell line–derived neurotrophic factor (GDNF) receptor RET have both been independently linked to the dopaminergic neuron degeneration that underlies Parkinson’s disease (PD). In the present study, we demonstrate that there is genetic crosstalk between parkin and the receptor tyrosine kinase RET in two different mouse models of PD. Mice lacking both parkin and RET exhibited accelerated dopaminergic cell and axonal loss compared with parkin-deficient animals, which showed none, and RET-deficient mice, in which we found moderate degeneration. Transgenic expression of parkin protected the dopaminergic systems of aged RET-deficient mice. Downregulation of either parkin or RET in neuronal cells impaired mitochondrial function and morphology. Parkin expression restored mitochondrial function in GDNF/RET-deficient cells, while GDNF stimulation rescued mitochondrial defects in parkin-deficient cells. In both cases, improved mitochondrial function was the result of activation of the prosurvival NF-κB pathway, which was mediated by RET through the phosphoinositide-3-kinase (PI3K) pathway. Taken together, these observations indicate that parkin and the RET signaling cascade converge to control mitochondrial integrity and thereby properly maintain substantia nigra pars compacta dopaminergic neurons and their innervation in the striatum. The demonstration of crosstalk between parkin and RET highlights the interplay in the protein network that is altered in PD and suggests potential therapeutic targets and strategies to treat PD.     

Renal transplantation in HLA sensitized patients: Traversing the immunological barrier

Successful renal transplantation across HLA barrier in sensitized individuals has been on the rise during the past decade, primarily due to improved desensitization regimes. The aim of this study was to share outcome of desensitization in renal transplant recipients with donor‐specific anti‐HLA antibodies (DSA). This was a retrospective analysis of all HLA immunized individuals who were prospective renal transplant recipients. All such patients underwent preconditioning as per the institutional desensitization protocol. Complement‐dependent cytoxicity‐based crossmatch (CDC‐XM), luminex‐based crossmatch (LM‐XM) and flowcytometry‐based crossmatch (FC‐XM) were done in all cases. If any of these tests turned out positive, single antigen bead assay (SAB) was performed. Desensitization for DSA was performed in 55 patients and all patients were followed‐up for 1 year to assess graft function and patient outcome. CDC‐XM being a less sensitive assay, could not detect incompatibility in 29 (52.73%) cases. After desensitization, even though SAB and LM‐XM results revealed an MFI within acceptable range, FC‐XM being an extremely sensitive assay, continued to give a positive result in eight (14.55%) cases. The mean ± SD number of pretransplant TPE were 3.44 ± 0.98 (2‐11). Out of 55, there were 10 patients who were lost to follow up. Patient and graft survival of 45 patients at 1 year was found to be 100%. Preconditioning for renal transplants in the form of immunosuppression with TPE is an extremely useful auxiliary for transplantation in HLA sensitized renal transplant recipients.     

Cathepsin E Promotes Pulmonary Emphysema via Mitochondrial Fission

Emphysema is characterized by loss of lung elasticity and irreversible air space enlargement, usually in the later decades of life. The molecular mechanisms of emphysema remain poorly defined. We identified a role for a novel cathepsin, cathepsin E, in promoting emphysema by inducing mitochondrial fission. Unlike previously reported cysteine cathepsins, which have been implicated in cigarette smoke-induced lung disease, cathepsin E is a nonlysosomal intracellular aspartic protease whose function has been described only in antigen processing. We examined lung tissue sections of persons with chronic obstructive pulmonary disease, a clinical entity that includes emphysematous change. Human chronic obstructive pulmonary disease lungs had markedly increased cathepsin E protein in the lung epithelium. We generated lung epithelial-targeted transgenic cathepsin E mice and found that they develop emphysema. Overexpression of cathepsin E resulted in increased E3 ubiquitin ligase parkin, mitochondrial fission protein dynamin-related protein 1, caspase activation/apoptosis, and ultimately loss of lung parenchyma resembling emphysema. Inhibiting dynamin-related protein 1, using a small molecule inhibitor in vitro or in vivo, inhibited cathepsin E-induced apoptosis and emphysema. To the best of our knowledge, our study is the first to identify links between cathepsin E, mitochondrial fission, and caspase activation/apoptosis in the pathogenesis of pulmonary emphysema. Our data expand the current understanding of molecular mechanisms of emphysema development and may provide new therapeutic targets.Emphysema is a major subset of chronic obstructive pulmonary disease (COPD) and is defined anatomically as the destruction of the distal lung parenchyma and enlargement of the air spaces. Pulmonary emphysema is one of the main causes of morbidity and death worldwide. The most studied factor in developing COPD has long been recognized to be cigarette smoking. However, only 10% to 20% of heavy smokers develop clinically significant COPD.^1,2 Importantly, recent studies indicate that complementary pathogenic mechanisms, such as proteolytic/antiproteolytic imbalance, oxidative stress, apoptosis, or altered innate immunity, are involved in the development and progression of alveolar destruction.^3–6Cathepsins have been implicated in mediating alveolar destruction via their proteolytic activity. Cathepsins are intracellular hydrolases and include serine proteases (cathepsins A and G), aspartic proteases (cathepsins D and E), and cysteine cathepsins (cathepsins B, C, F, H, K, L, O, S, V, X, and W). Cathepsin E (Cat E), a nonlysosomal intracellular aspartic protease, is homologous to aspartic protease cathepsin D, a major proteolytic activity in the lysosomal component.⁷ Recent studies have reported that Cat E plays an important role in antigen processing via the major histocompatibility complex class II pathway, host defense against cancer cells and invading microorganisms, gastric differentiation, and development of signet-ring cell carcinoma.^8–12 However, Cat E has not been linked to lung disease.Human lung sections from persons with COPD indicated increased expression of Cat E protein in the lung epithelial cells. To investigate if increased expression of lung epithelial Cat E could lead to emphysema, we generated lung-targeted constitutive and inducible Cat E transgenic (Tg) mice. Our data indicated that inducible Cat E Tg mice developed emphysema-like lung changes as early as 1 week. We noted robust caspase 3 activation, and, when mice were administered a caspase inhibitor, emphysema was prevented. To our surprise, we did not find changes in caspases usually associated with caspase 3 activation, such as caspases 8 and 9, in Cat E Tg mice. Instead, we found significant induction of a mitochondrial fission protein, dynamin-related protein 1 (Drp1). When we inhibited Drp1 in Cat E Tg mice with Mdivi-1, a small molecule Drp1 inhibitor, we completely abolished the development of emphysema. Collectively, our data indicate that increased Cat E is a clinically relevant finding in human COPD and invoke a novel role for Cat E in mitochondrial fission-induced emphysema.