Clinical and radiological features of Mycobacterium kansasii and other NTM infections

SummaryBackgroundMycobacterium kansasii infection is one of the most common causes of nontuberculous mycobacterial lung disease in the world. However, it is not possible to differentiate completely between M. kansasii and other nontuberculous mycobacteria (NTM) because of a lack of direct comparative studies. This retrospective study sought to identify their clinical and radiological features systematically.MethodsThe sample included 98 consecutive patients with a culture-positive diagnosis of NTM infection, derived from the databases of the Laboratory of Microbiology of a tertiary medical center and two outpatient tuberculosis centers. Sixty-four patients had M. kansasii infection. All patients fulfilled disease criteria for treatment. Data on patient background and clinical features were collected, and chest radiographs were evaluated.ResultsIn the M. kansasii group, n = 27 (42%) were native-born Israelis compared to 9.4% (n = 3) of all other NTM groups (p = 0.0001). Similar rates of co-morbid diseases, including diabetes mellitus, heart disease, lung diseases, and malignancy were noted in both groups. Old TB was less common in the M. kansasii group compared to the other NTM (3.1% vs. 23.5%, p = 0.003). Clinical symptoms were significantly more common in patients with M. kansasii infection. On radiological study, M. kansasii infection was associated with more cavitations and unilaterality. Patients with M. kansasii infection had a higher likelihood of right upper lobe disease (p = 0.001). Pleural effusions and lymphadenopathy were found only in a few patients in each group.ConclusionMajor differences in the epidemiologic and clinical features of M. kansasii infection and other NTM have important diagnostic and clinical implications

Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis

Asymmetric Free-Space Light Transport at Nonlinear Metasurfaces

Asymmetric light transport has significantly contributed to fundamental science and revolutionized advanced technology in various aspects such as unidirectional photonic devices, optical diodes, and isolators. While metasurfaces mold wave fronts at will with an ultrathin flat optical element, asymmetric transport of light cannot be fundamentally achieved by any linear system including linear metasurfaces. We report asymmetric transport of free-space light at nonlinear metasurfaces upon transmission and reflection. Moreover, we theoretically derive the nonlinear generalized Snell\u27s laws that were experimentally confirmed by the anomalous nonlinear refraction and reflection. The asymmetric transport at optically thin nonlinear interfaces is revealed by the concept of a reversed propagation path. Such an asymmetric transport at metasurfaces opens a new paradigm for free-space ultrathin lightweight optical devices with one-way operation including unrivaled optical valves and diodes

Flexible bronchoscopic management of benign tracheal stenosis: long term follow-up of 115 patients

<p>Abstract</p> <p>Background</p> <p>Management of benign tracheal stenosis (BTS) varies with the type and extent of the disease and influenced by the patient's age and general health status, hence we sought to investigate the long-term outcome of patients with BTS that underwent minimally invasive bronchoscopic treatment.</p> <p>Methods</p> <p>Patients with symptomatic BTS were treated with flexible bronchoscopy therapeutic modalities that included the following: balloon dilatation, laser photo-resection, self-expanding metal stent placement, and High-dose rate endobronchial brachytherapy used in cases of refractory stent-related granulation tissue formation.</p> <p>Results</p> <p>A total of 115 patients with BTS and various cardiac and respiratory co-morbidities with a mean age of 61 (range 40-88) were treated between January 2001 and January 2009. The underlining etiologies for BTS were post - endotracheal intubation (N = 76) post-tracheostomy (N = 30), Wegener's granulomatosis (N = 2), sarcoidosis (N = 2), amyloidosis (N = 2) and idiopathic BTS (N = 3). The modalities used were: balloon dilatation and laser treatment (N = 98). Stent was placed in 33 patients of whom 28 also underwent brachytherapy. Complications were minor and mostly included granulation tissue formation. The overall success rate was 87%. Over a median follow-up of 51 months (range 10-100 months), 30 patients (26%) died, mostly due to exacerbation of their underlying conditions.</p> <p>Conclusions</p> <p>BTS in elderly patients with co-morbidities can be safely and effectively treated by flexible bronchoscopic treatment modalities. The use of HDR brachytherapy to treat granulation tissue formation following successful airway restoration is promising.</p

Effectiveness of third-class biologic treatment in crohn’s disease : A multi-center retrospective cohort study

Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Background: Multiple studies have described the effectiveness of ustekinumab (UST) and vedolizumab (VDZ) in patients with Crohn’s disease (CD) failing anti-Tumor necrosis factors (TNFs); however, the effectiveness of VDZ or UST as a third-class biologic has not yet been described. Aims and Methods: In this retrospective multicenter cohort study, we aimed to investigate the effectiveness of VDZ and UST as a third-class biologic in patients with CD. Results: Two-hundred and four patients were included; 156/204 (76%) patients received VDZ as a second-and UST as a third-class therapy (group A); the remaining 48/204 (24%) patients received UST as a second-and VDZ as a third-class therapy (group B). At week 16–22, 87/156 (55.5%) patients and 27/48 (56.2%) in groups A and B, respectively, responded to treatment (p = 0.9); 41/156 (26.2%) and 15/48 (31.2%) were in clinical remission (p = 0.5). At week 52; 89/103 (86%) patients and 25/29 (86.2%) of the patients with available data had responded to third-class treatment in groups A and B, respectively (p = 0.9); 31/103 (30%) and 47/29 (24.1%) were in clinical remission (p = 0.5). Conclusion: Third-class biological therapy was effective in more than half of the patients with CD. No differences in effectiveness were detected between the use of VDZ and UST as a third-class agent.Peer reviewe

Effectiveness of third-class biologic treatment in Crohn's disease : a multi-center retrospective cohort study

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A Myo6 Mutation Destroys Coordination between the Myosin Heads, Revealing New Functions of Myosin VI in the Stereocilia of Mammalian Inner Ear Hair Cells

Myosin VI, found in organisms from Caenorhabditis elegans to humans, is essential for auditory and vestibular function in mammals, since genetic mutations lead to hearing impairment and vestibular dysfunction in both humans and mice. Here, we show that a missense mutation in this molecular motor in an ENU-generated mouse model, Tailchaser, disrupts myosin VI function. Structural changes in the Tailchaser hair bundles include mislocalization of the kinocilia and branching of stereocilia. Transfection of GFP-labeled myosin VI into epithelial cells and delivery of endocytic vesicles to the early endosome revealed that the mutant phenotype displays disrupted motor function. The actin-activated ATPase rates measured for the D179Y mutation are decreased, and indicate loss of coordination of the myosin VI heads or ‘gating’ in the dimer form. Proper coordination is required for walking processively along, or anchoring to, actin filaments, and is apparently destroyed by the proximity of the mutation to the nucleotide-binding pocket. This loss of myosin VI function may not allow myosin VI to transport its cargoes appropriately at the base and within the stereocilia, or to anchor the membrane of stereocilia to actin filaments via its cargos, both of which lead to structural changes in the stereocilia of myosin VI–impaired hair cells, and ultimately leading to deafness

Activation of an NLRP3 Inflammasome Restricts Mycobacterium kansasii Infection

Mycobacterium kansasii has emerged as an important nontuberculous mycobacterium pathogen, whose incidence and prevalence have been increasing in the last decade. M. kansasii can cause pulmonary tuberculosis clinically and radiographically indistinguishable from that caused by Mycobacterium tuberculosis infection. Unlike the widely-studied M. tuberculosis, little is known about the innate immune response against M. kansasii infection. Although inflammasome activation plays an important role in host defense against bacterial infection, its role against atypical mycobacteria remains poorly understood. In this report, the role of inflammasome activity in THP-1 macrophages against M. kansasii infection was studied. Results indicated that viable, but not heat-killed, M. kansasii induced caspase-1-dependent IL-1β secretion in macrophages. The underlying mechanism was found to be through activation of an inflammasome containing the NLR (Nod-like receptor) family member NLRP3 and the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). Further, potassium efflux, lysosomal acidification, ROS production and cathepsin B release played a role in M. kansasii-induced inflammasome activation. Finally, the secreted IL-1β derived from caspase-1 activation was shown to restrict intracellular M. kansasii. These findings demonstrate a biological role for the NLRP3 inflammasome in host defense against M. kansasii

Role of siroliumus, a novel immunosuppressive drug in heart and lung transplantation

AbstractLung and heart transplantation has become an accepted therapeutic option for patients with end-stage disease. However, the calcineurin-inhibitor-based immunosuppression often causes renal impairment. Therefore, sirolimus, a novel immunosuppressive agent, may serve as an alternative or complementary agent to calcineurin inhibitors. The aim of this review was to summarize the role of sirolimus in lung and heart transplantation. Although only a few, small studies have been conducted so far, the drug's mechanisms of action and low-toxicity profile make it a highly promising option