Amiodarone Induced Interstitial and Organizing Pneumonia Reversed with Steroids.

Amiodarone is a widely used antiarrhythmic agent for supraventricular and ventricular tachyarrhythmias. It is known to cause pulmonary toxicity, which can manifest in a variety of presentations, ranging from asymptomatic to fatal. We present a case of chronic interstitial pneumonia with organizing pneumonia induced by amiodarone that was successfully treated with drug cessation and use of corticosteroids. The patient experienced complete resolution of symptoms and full recovery of lung function after the course of steroids.

Microglia's heroic battle against neurodegeneration.

In this issue of Neuron, Chadarevian et al.1 and Munro et al.2 demonstrate how the absence of homeostatic microglia leads to severe neuropathologies, including axonal spheroids, calcifications, myelination abnormalities, and gliosis, associated with leukoencephalopathy and age-related neurodegeneration. Transplantation of healthy microglia can reverse these conditions, opening new avenues for therapeutic research.

Use of Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction After Cardiac Transplantation: Results of an A Priori Ventless Approach.

Primary graft dysfunction (PGD) after cardiac transplantation is a devastating complication with increasing frequency lately in the setting of donation after circulatory death (DCD). Severe PGD is commonly treated with extracorporeal membrane oxygenation (ECMO) using central or peripheral cannulation. We retrospectively reviewed the outcomes of PGD after cardiac transplantation requiring ECMO support at our center from 2015 to 2020, focused on our now preferential approach using peripheral cannulation without a priori venting. During the study period, 255 patients underwent heart transplantation at our center and 26 (10.2%) of them required ECMO for PGD. Of 24 patients cannulated peripherally 19 (79%) were alive at 30 days and 17 (71%) 1 year after transplant; two additional patients underwent central ECMO cannulation due to unfavorable size of femoral vessels and concern for limb ischemia. Successful decannulation with full graft function recovery occurred in 22 of 24 (92%) patients cannulated peripherally. Six of them had an indwelling intra-aortic balloon pump placed before the transplantation. None of the other 18 patients received a ventricular vent. In conclusion, the use of an a priori peripheral and ventless ECMO approach in patients with PGD after heart transplant is an effective strategy associated with high rates of graft recovery and survival.

A RP-HPLC Method for the Analysis of Neostigmine Methylsulfate and Process-Related Impurities, Forced Degradation Studies, in the Injection Formulation.

Neostigmine methylsulfate is an anticholinesterase agent and is clinically used for treating myasthenia gravis. It is also used for reversing nondepolarising neuromuscular blocking agents. Neostigmine methylsulfate may be administered by intravenous, intramuscular, or subcutaneous injection. In this research paper, a distinct stability-indicating reverse phase HPLC method was developed and validated for the quantitative determination of related impurities and degradation impurities in neostigmine methylsulfate API and injection formulation. The specific objective was to improve the resolution between European Pharmacopoeia listed impurity A and impurity B and degradation impurity of neostigmine methylsulfate API and injection formulation. The analysis was performed using Kromasil C18 column at 30°C of column oven temperature with phosphate-buffer/acetonitrile in a gradient mode. The RP-HPLC method was developed and validated for in-house neostigmine methylsulfate synthesis process sample and injection formulation. The injection formulation sample was studied for accelerated stability, temperature cycling stability, and photostability. The validation studies for neostigmine methylsulfate synthesis process API were studied using impurity A, impurity B, and impurity C. The analytical method validation parameters studied were specificity, precision, linearity, limit of detection, limit of quantitation, accuracy, and robustness. The API and the injection formulation were subjected to forced degradation under acid, alkali, oxidation, and photolytic and thermal conditions. The proposed method showed a significantly improved RRT (Relative Retention Time) of impurity A and impurity B with a resolution greater than 1.5. The developed method eliminates the use of an ion-pairing agent and thereby a good performance of column was established.

Cardiac Sympathetic Denervation for Refractory Ventricular Arrhythmia in Continuous-Flow Left Ventricular Assist Device.

Cardiac sympathetic denervation has been shown to reduce sustained ventricular arrhythmias and implantable cardioverter-defibrillator shocks by inhibiting sympathetic outflow to the heart. We describe the first case to our knowledge of cardiac sympathetic denervation in the left ventricular assist device population. (Level of Difficulty: Advanced.).

A Validated RP-HPLC Stability Method for the Estimation of Chlorthalidone and Its Process-Related Impurities in an API and Tablet Formulation.

Low-dose thiazide and thiazide-like diuretics are widely used as first-line therapy for hypertension. Chlorthalidone, a monosulfamyl diuretic, is frequently prescribed in cases of hypertension and congestive heart failure. In this research paper, an improved reverse-phase HPLC method was developed for the simultaneous identification and quantitation of pharmacopoeia-listed and in-house process- and degradation-related impurities of chlorthalidone in bulk drug and formulations. Chromatographic separation was carried out on a C8 column (250 × 4.6 mm; '5 µm particle size) at a flow rate of 1.4 mL/min with a 220 nm detection wavelength. Mobile phase A consisted of buffer solution (diammonium hydrogen orthophosphate (10 mM, pH 5.5)) and methanol at a 65 : 35 ratio (v/v), and mobile phase B consisted of buffer solution and methanol at a 50 : 50 ratio (v/v). The API and formulation were subjected to stress conditions such as acid, alkali, oxidation, thermal, and photolytic conditions. Validation studies for the in-house process impurities were performed for specificity, limit of detection (LOD), limit of quantitation (LOQ), linearity, precision, accuracy, and robustness. Thus, an improved RP-HPLC method capable of good separation of all known and unknown impurities with acceptable resolution and tailing factor was developed.

Influence of nitrogen/phosphorus-doped carbon dots on polyamide thin film membranes for water vapor/N2 mixture gas separation.

Nanoparticles have been attracting attention because they can significantly improve the performance of membranes when added in small amounts. In this study, the effect of polyamide membranes incorporating hydrophilic nitrogen/phosphorus-doped carbon dots (NP-CDs) to enhance water vapor/N2 separation has been investigated. NP-CD nanoparticles with many hydrophilic functional groups are synthesized from chitosan by a one-pot green method and introduced to the surface of the polysulfone (PSf) substrates by interfacial polymerization reaction. The mean particle diameter of NP-CDs, estimated from transmission electron microscopy images, is 2.6 nm. By adding NP-CDs (0-1.5 wt%) to the polyamide layer, the contact angles of the membranes dramatically decreased from 65° (PSf) to <9° (thin film nanocomposite (TFN)), which means that the TFN membranes become significantly hydrophilic. From the water vapor separation results, the addition of NP-CDs in the polyamide layer improves the water vapor permeance from 1511 (thin film composite (TFC) without nanoparticles) to 2448 GPU (TFN with 1.0 wt% NP-CD loading, CD-TFN(1.0)) and the water vapor/N2 selectivity from 73 (TFC) to 854 (CD-TFN(1.0)). To our knowledge, this is the first study of highly functionalized NP-CD-incorporated polyamide membranes to enhance water vapor separation.

Mitral valve vegetation diagnosed with oesophageal ultrasound with bronchoscope (EUS-B).

Oesophageal ultrasound with bronchoscope (EUS-B) is designed to evaluate mediastinal structures. We describe a case of a 78-year-old woman who presented with altered mental status for 2 weeks. CT head revealed a subacute infarct in the right middle cerebral artery distribution. She was also found to have a lung mass on chest imaging. EUS-B-guided fine needle aspiration demonstrated the presence of adenocarcinoma in station 7 lymph node and in the mass. Immunohistochemistry confirmed it to be a lung primary as the Thyroid Transcription Factor-1 (TTF-1) was strongly positive. During the procedure, the cardiac valves were evaluated, and a mitral valve vegetation was noted. Formal echocardiography confirmed the presence of the vegetation. During hospital stay, the patient developed fever. Her blood cultures grew oxacillin-resistant Staphylococcus aureus. She was subsequently treated for infective endocarditis. We suggest that the use of EUS-B to routinely scan adjacent structures during a procedure may help obtain additional clinical information that may be critical to patient management.

Utilization and Predictors of Electrical Cardioversion in Patients Hospitalized for Atrial Fibrillation.

Atrial fibrillation (AF) is a common arrhythmia in adults associated with thromboembolic complications. External electrical cardioversion (DCCV) is a safe procedure used to convert AF to normal sinus rhythm. We sought to study factors that affect utilization of DCCV in hospitalized patients with AF. The study sample was drawn from the Nationwide Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project in the United States. Patients with a primary discharge diagnosis of AF that received DCCV during hospitalization in the years 2000-2010 were included. An estimated 2,810,530 patients with a primary diagnosis of AF were hospitalized between 2001 and 2010, of which 1,19,840 (4.26%) received DCCV. The likelihood of receiving DCCV was higher in patients who were males, whites, privately insured, and aged < 40 years and those with fewer comorbid conditions. Higher CHADS2 score was found to have an inverse association with DCCV use. In-hospital stroke, in-hospital mortality, length of stay, and cost for hospitalization were significantly lower for patients undergoing DCCV during AF related hospitalization. Further research is required to study the contribution of other disease and patient related factors affecting the use of this procedure as well as postprocedure outcomes.

Thinking outside the box: a middle-aged man with new-onset dyspnoea on exertion and pedal oedema.

We describe a diagnostic dilemma in a middle-aged man presenting with dyspnoea and bilateral pedal oedema who had been diagnosed with right heart failure based on clinical evidence. The evaluation for aetiology eventually led to discovery of an unusual extrathoracic cause, a left-to-right communication in the renal vasculature. Renal arteriovenous fistulae are rare and can be congenital, acquired or idiopathic. A left-to-right shunt typically presents with high-output cardiac failure involving the left and right sides of the heart. An atypical feature of this case was the finding of overt right heart failure in the setting of a normal left heart. Such a presentation has only been described in a few isolated case reports. Diagnostic approaches include CT angiography and cardiac catheterisation for haemodynamic measurements. The primary treatment options for arteriovenous fistulae are medical management, arterial embolisation and surgical repair.

Myasthenia gravis masquerading as dysphagia: unveiled by magnesium infusion.

Myasthenia gravis (MG) is a neuromuscular disorder that typically affects the ocular, bulbar, neck, proximal limbs and respiratory muscles. Dysphagia can occasionally be the only presenting symptom leading to extensive but ultimately futile gastrointestinal workup. Delay in diagnosis and use of certain pharmacological agents in the interim can lead to a myasthenic crisis, which though diagnostic is life threatening. We document a case of dysphagia as the only symptom of myasthenia, diagnosed after a magnesium infusion precipitated myasthenic crisis. A 70-year-old Caucasian woman who had had progressive dysphagia for 2 years, for which multiple oesophageal dilations were performed. During a hosptalisation for further gastrointestinal workup, she went into myasthenic crisis (respiratory failure) after receiving magnesium replacement. She required ventilatory support and received five plasma exchange (PLEX) treatments after myasthenia was confirmed by the detection of high antiacetylcholine receptor antibody. Though her symptoms improved, she had a prolonged hospital stay (25 days) and required 18 days of mechanical ventilation. This underscores the morbidity associated with a delay in diagnosis of this condition. This case report suggests that neuromuscular causes should be considered early in elderly patients presenting with dysphagia. Timely diagnosis, initiation of management and avoidance of drugs that affect neuromuscular transmission may help reduce the morbidity and mortality associated with myasthenic crisis.

Molecular characterization of Indian isolate of peanut mottle virus and immunodiagnosis using bacterial expressed core capsid protein.

Peanut mottle virus (PeMoV), a seed borne potyvirus was recorded in India in 1978, however the virus was not characterized at molecular level. In the present study, an isolate of PeMoV infecting peanut in southern India was characterized based on host reactions and coat protein (CP) gene sequence, which revealed that the Indian isolate was very close to a peanut isolate reported from Israel and distinct from pea isolate reported from USA. The core region of CP gene that contained majority of the predicted epitopes was successfully expressed (1.75 mg/l) in Escherichia coli as a 22 kDa protein. A high titer polyclonal antibody (PAb) to the expressed core CP was produced, which efficiently detected PeMoV. The antiserum was useful in specific detection of PeMoV as it showed negligible cross reactivity with the other potyviruses e.g., peanut stripe virus, potato virus Y, papaya ringspot virus and onion yellow dwarf virus. The PAb was validated in ELISA using 1,169 field and greenhouse samples of peanut which showed 1.85-26.3 % incidence of PeMoV in peanut seed multiplication field during 2011-2012. This is the first report of immunodiagnosis of PeMoV with a PAb to recombinant core CP of PeMoV.

Highly efficient immunodiagnosis of Large cardamom chirke virus using the polyclonal antiserum against Escherichia coli expressed recombinant coat protein.

Large cardamom chirke virus (LCCV), genus Macluravirus, family Potyviridae is an important constrain in large cardamom production in India. Purification of LCCV from large cardamom tissues is difficult and therefore immunodiagnostic reagents are not available. In the present study, we have successfully expressed coat protein (CP) gene of LCCV in Escherichia coli. The purification of expressed protein by Ni-NTA affinity chromatography was inefficient due to precipitation of protein during renaturation. We have optimized a simple, inexpensive and efficient method for purification of the expressed CP through gel extraction with 5 % SDS followed by renaturation in Milli-Q water, which resulted in high yield (4.7 mg/ml) and good quality of the protein. A higher titer (1:256,000) polyclonal antibody (PAb) to the recombinant CP was produced, which strongly recognized LCCV in crude leaf extract and showed minimal background reaction with the healthy leaf extract in enzyme linked immunosorbent assay (ELISA) and dot immunobinding assay (DIBA). The sensitivities of the ELISA and DIBA were 5 and 0.1 ng of expressed protein, respectively. Both the ELISA and DIBA were validated with 100 % accuracy in detecting LCCV in field samples. The PAb differentiated Cardamom mosaic virus, another close relative of LCCV. Our study is first to report highly efficient immunodiagnosis with PAb to E. coli expressed recombinant CP of a virus under the genus Macluravirus. The antigen expression construct and PAb developed in the present study will be useful in production of virus free planting materials of large cardamom.