A Comprehensive Review on Chemistry and Biology of Tafamidis in Transthyretin Amyloidosis.

Transthyretin amyloid cardiomyopathy and Transthyretin amyloid peripheral neuropathy are progressive disease conditions caused by Transthyretin amyloidosis (ATTR) fibril infiltration in the tissue. Transthyretin (TTR) protein misfolding and amyloid fibril deposits are pathological biomarkers of ATTR-related disorders. There are various treatment strategies targeting different stages in pathophysiology. One such strategy is TTR tetramer stabilization. Recently, a new TTR tetramer stabilizer, tafamidis, has been introduced that reduces the protein misfolding and amyloidosis and, consequently, disease progression in ATTR cardiomyopathy and peripheral neuropathy. This review will provide a comprehensive overview of the literature on tafamidis discovery, development, synthetic methods, pharmacokinetics, analytical methods and clinical trials. Overall, 7 synthetic methods, 5 analytical methods and 23 clinical trials have been summarized from the literature.

A Retrospective Observational Study of Domiciliary Oxygen Usage in a Subset of Veterans.

BACKGROUND: Long-term oxygen therapy (LTOT) delivered continuously is known to decrease mortality in patients with COPD and who are hypoxemic; however, supportive data for LTOT use in patients without COPD is lacking. In addition, many patients may be prescribed LTOT without a definitive etiology for hypoxemia. First, we investigated the diagnoses for which oxygen was prescribed to a sample of veterans and whether each diagnosis was supported by confirmatory testing. Second, we looked at the proportion of subjects who were prescribed non-continuous therapy. METHODS: We retrospectively studied subjects prescribed domiciliary oxygen at the Veterans Administration Western New York Healthcare System. The subjects who met inclusion criteria were identified by using a computerized patient record system; data were collected on subject characteristics, oxygen prescription information, diagnosis for hypoxia, and diagnostic workup. Descriptive data were presented as mean ± SD and median (range). Statistical analysis was performed by using the chi-square test and an unpaired t test. RESULTS: A total of 494 subjects were included: 96.8% men, mean ± SD ages 74.2 ± 10.8 y. Most of the subjects were prescribed oxygen as out-patients (68.5%). A total of 335 (67.8%) were prescribed oxygen for continuous therapy, 72 (14.1%) for nocturnal therapy, 50 (10.1%) for exertion, and 30 (6.1%) for both exertion and nocturnal use. At 3 months, 19.6% of the initial cohort had oxygen discontinued. In those subjects with oxygen continued at 3 months, COPD was the most common diagnosis (63.6%), of which 76.1% had pulmonary function tests (PFTs), with 85.7% showing obstruction on spirometry. CONCLUSIONS: Results of our study showed a 99.4% adherence to Medicare criteria for domiciliary oxygen prescription. Also, 30.3% of the subjects were prescribed LTOT for exertional or nocturnal desaturation or both. Repeated testing at 3 months identified subjects who no longer required oxygen. COPD was the most common etiology for domiciliary oxygen. A small proportion of the subjects (6.9%) were prescribed oxygen without underlying etiology for hypoxia. Exertional and/or nocturnal oxygen prescription was common, and further research to elucidate its utility is clearly warranted.

Design and evaluation of topical solid dispersion composite of voriconazole for the treatment of ocular keratitis.

Aim: The objective of present investigation was to increases solubility of voriconazole by using solid dispersion techniques and the development of solid dispersion-based voriconazole ophthalmic solutions. Materials & methods: The saturation solubility of solid dispersion containing polyvinylpyrrolidone K90 (PVPK-90) was found to increase the solubility of voriconazole compare other carrier like polyethylene glycol and Polyvinylpyrrolidone K 30 (PVPK-30). Solid dispersion of voriconazole was characterized by saturation solubility, Fourier-transform infrared spectroscopy and Differential scanning calorimetry study. Results & conclusion: The Fourier-transform infrared spectroscopy and Differential scanning calorimetry studies of voriconazole-based solid dispersion confirmed the complete changes in original polymorphic form of voriconazole. The antifungal assay showed that the maximum zone of inhibition was produced from optimized ophthalmic formulation containing sodium alginate as compared with other formulations and marketed eye drops.

Airway Obstruction Caused by Iron Pill Aspiration: An Interventional Pulmonology Approach to Prevent Surgery.

Iron Pill Aspiration (IPA) is a challenging medical condition that requires prompt management to prevent detrimental outcomes. One of the most serious complications of IPA is airway inflammation which commonly leads to severe obstruction. Airway complications may require surgical intervention including the resection of the affected lung. Prompt recognition and management of IPA can reduce the risk of airway complications and may prevent the need of a surgical intervention. Bronchoscopic management entails the use of flexible and rigid bronchoscopes along with balloon bronchoplasty, ablation of the inflammatory tissue causing obstruction and airway stenting. In this report, we describe a case of severe airway obstruction secondary to iron pill aspiration with favourable outcome following bronchoscopic multimodalities intervention including temporary airway stenting.

Management of Benign Pleural Effusions Using Indwelling Pleural Catheters: A Systematic Review and Meta-analysis.

BACKGROUND: The indwelling pleural catheter (IPC), which was initially introduced for the management of recurrent malignant effusions, could be a valuable management option for recurrent benign pleural effusion (BPE), replacing chemical pleurodesis. The purpose of this study is to analyze the efficacy and safety of IPC use in the management of refractory nonmalignant effusions. METHODS: We conducted a systematic review and meta-analysis on the published literature. Retrospective cohort studies, case series, and reports that used IPCs for the management of pleural effusion were included in the study. RESULTS: Thirteen studies were included in the analysis, with a total of 325 patients. Congestive heart failure (49.8%) was the most common cause of BPE requiring IPC placement. The estimated average rate of spontaneous pleurodesis was 51.3% (95% CI, 37.1%-65.6%). The estimated average rate of all complications was 17.2% (95% CI, 9.8%-24.5%) for the entire group. The estimated average rate of major complications included the following: empyema, 2.3% (95% CI, 0.0%-4.7%); loculation, 2.0% (95% CI, 0.0%-4.7%); dislodgement, 1.3% (95% CI, 0.0%-3.7%); leakage, 1.3% (95% CI, 0.0%-3.5%); and pneumothorax, 1.2% (95% CI, 0.0%-4.1%). The estimated average rate of minor complications included the following: skin infection, 2.7% (95% CI, 0.6%-4.9%); blockage and drainage failure, 1.1% (95% CI, 0.0%-3.5%); subcutaneous emphysema, 1.1% (95% CI, 0.0%-4.0%); and other, 2.5% (95% CI, 0.0%-5.2%). One death was directly related to IPC use. CONCLUSIONS: IPCs are an effective and viable option in the management of patients with refractory BPE. The quality of evidence to support IPC use for BPE remains low, and high-quality studies such as randomized controlled trials are needed.

Successful bronchoscopy in a pregnant patient with plastic bronchitis.

Plastic bronchitis is a rare disorder, characterized by formation of thick fibrinous bronchial casts which can obstruct the airway and present as a life threatening emergency (1). It is more common in the pediatric population after corrective or palliative surgery for congenital heart disease like fontan procedure but has rarely been reported in adults as well (1). Pregnancy is a relative contraindication for bronchoscopy. Bronchoscopy in the pregnant patient poses significant risks as manipulation of the airway can lead to impaired oxygenation and ventilation. In addition, the drugs used during this procedure to provide sedation can have a direct impact on the developing fetus (2). In spite of these risks bronchoscopy should not be withheld in an emergent situation as it can be a lifesaving measure. We report a case of successful bronchoscopy using Propofol as the sedating agent in a pregnant female with plastic bronchitis who presented with respiratory distress.

Endobronchial Ultrasound Bronchoscope Damage.

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration is an effective, safe, and cost-effective diagnostic bronchoscopy technique for the work-up of mediastinal lymphadenopathy. Concern has been raised, however, about the high cost of convex-probe EBUS bronchoscope repairs. The damage is usually due to breakage of the insertion tube (the flexible part that is advanced into the airways), moisture invasion and damages to the working channel, image guide bundle, or umbilical cord. Understanding the root cause of EBUS scope damage is important for its prevention. We describe 2 unusual cases of EBUS scope damage. In the first case, the distal black rubber covering of the EBUS scope insertion tube was damaged due to friction with the edge of an endotracheal tube and in the second case, the EBUS scope insertion tube was angulating laterally instead of vertically during the flexion maneuver, probably due to scope manipulation while wedged tightly in a segmental bronchus.

Cardiovascular mortality in obstructive sleep apnoea treated with continuous positive airway pressure or oral appliance: an observational study.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the long-term cardiovascular mortality in patients with severe obstructive sleep apnoea (OSA) treated with either continuous positive airway pressure (CPAP) or mandibular advancing device (MAD). METHODS: A non-concurrent cohort study of 570 subjects with severe OSA (apnoea/hypopnoea index (AHI) ≥ 30/h) and a control group of 269 subjects (AHI < 5/h) were followed up for a median of 79 months (interquartile range 76-88 months). All patients received CPAP initially. MAD was offered for those who were non-adherent to CPAP. The endpoint was cardiovascular death. RESULTS: Two hundred and eight control subjects, 177 patients treated with CPAP, 72 with MAD and 212 who declined treatment were analysed. Forty-two patients had a fatal cardiovascular event during the course of the study. The non-apnoeic group had the lowest cardiovascular death rate (0.28 per 100 person-years (95% confidence interval (CI): 0.08-0.71)) followed by the CPAP-treated (0.56 per 100 person-years (95% CI: 0.20-1.23)) and the MAD-treated OSA group (0.61 per 100 person-years (95% CI: 0.13-1.78)), with the highest cardiovascular mortality rate observed in the untreated OSA group (2.1 per 100 person-years (95% CI: 1.37-2.92)). Although residual AHI for MAD-treated patients was significantly higher than CPAP-treated patients (16.3 ± 5.1/h vs. 4.5 ± 2.3/h; P < 0.001), there was no difference in cardiovascular death rate between the two groups (hazard ratio 1.08 (95% CI: 0.55-1.74); P = 0.71). CONCLUSIONS: Both CPAP and MAD may be equally effective therapy in reducing the risk of fatal cardiovascular events in patients with severe OSA.

Vincristine in high-grade glioma.

AIM: Numerous chemotherapeutics are used in the treatment of high-grade glioma (HGG). The purpose of this study was to evaluate the therapeutic value of vincristine (VCR) in the treatment of HGGs. MATERIALS AND METHODS: A meta-analysis of HGG studies was performed to evaluate and compare the efficacy of chemotherapy drugs using observed and predicted median overall survival and survival gain as previously described. RESULTS: Patient cohorts treated with VCR-containing-regimens had a significant survival gain advantage over cohorts treated with other chemotherapy drugs (p<0.0001). VCR was most effective in treating newly diagnosed adult (p<0.0001) and elderly (p=0.0001) patients. When VCR was combined with nimustine, carmustine, cytarabine or etoposide, the effect was antagonistic, but when VCR was combined with lomustine, procarbazine, cyclophosphamide, dacarbazine, hydroxyurea, or cisplatin it was synergistic. CONCLUSION: Results from this study suggest that VCR should be included in chemotherapy regimens for patients being treated for newly diagnosed or recurrent HGG.