Lessons from a case with stiff left atrial syndrome complicated by iatrogenic inter-atrial shunts: a case report.

Background: In patients with stiff left atrial (LA) syndrome, reservoir function is significantly impaired due to extensive LA fibrosis; consequently, the increase in LA pressure during haemodynamic stress is prominent, easily leading to pulmonary venous hypertension and subsequent pulmonary congestion, and eventually results in intractable heart failure. Case summary: A 79-year-old female with mitral stenosis and atrial fibrillation underwent valve replacement, Cox-Maze IV procedure, LA plication, and appendage ligation 4 years prior to presentation. Thereafter, she underwent a total of two catheter ablation procedures for recurrent atrial tachycardia. Transthoracic echocardiography revealed two continuous colour jets across the interatrial septum, with a peak pressure gradient of 23 mmHg, which was consistent with the residual puncture hole at the catheter ablation procedures. Although transoesophageal echocardiography showed no evidence of prosthetic valve dysfunction, the pulmonary venous flow signal showed a significantly blunted systolic forward flow, extremely small retrograde reversal flow during atrial contraction, and prominent diastolic flow velocities, all of which indicated significantly impaired LA function. Cardiac catheter examination revealed a characteristic pulmonary capillary wedge pressure waveform, which consisted of a steep ascending limb of v wave with a large peak, consistent with stiff LA syndrome. Discussion: Treatment of patients with stiff LA syndrome is quite challenging and restricted to the use of diuretics only, which has limited efficacy and eventually results in intractable heart failure. In this case, owing to the inter-atrial pressure-relieving gateway, the patient was only mildly symptomatic despite the existence of a non-compliant LA.

Involvement of neutrophil extracellular traps in the pathogenesis of glomerulonephritis in a case of systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome.

Systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are autoimmune diseases that often cause rapidly progressive glomerulonephritis, with neutrophil extracellular traps (NETs) involved in their pathogenesis. However, the involvement of NETs in the renal damage caused by SLE/AAV overlap syndrome has not been clarified yet. In this study, we detected renal deposition of NETs in a patient with SLE/AAV overlap syndrome. In addition, a significantly increased level of NET-inducing activity was observed in the patient's serum, which improved with treatment. On the other hand, a markedly lower level of NET degradation was observed in the patient's serum as compared to healthy subjects' sera, without any posttreatment changes. These findings suggest that NETs may play a role in the pathogenesis of renal injury associated with SLE/AAV overlap syndrome.

Evaluation of highly branched cyclic dextrin in inhalable particles of combined antibiotics for the pulmonary delivery of anti-tuberculosis drugs.

This work aims to identify a suitable formulation for the pulmonary delivery of combinations of inhalational drugs using highly branched cyclic dextrin (HBCD) macromolecules. We compared the effectiveness between powders prepared from HBCD with those prepared from five alternative excipients (lactose, maltose, sucrose, ß-cyclodextrin and methyl ß-cyclodextrin) in the pulmonary delivery of a single-dosage form of two anti-tuberculosis drugs (isoniazid and rifampicin). Fine particles of untreated active pharmaceutical ingredients (APIs) and combination products using excipients were prepared by spray drying. Rifampicin, a hydrophobic compound, was dissolved in ethanol, whereas isoniazid, a hydrophilic compound combined with either HBCD or an alternative excipient was dissolved in water. This was followed by the preparation of the spray-dried particle formulations (SDPs). The SDPs were characterised in terms of particle size, surface morphology, drug content, specific surface area, powder X-ray diffraction and inhalational properties. The addition of either an excipient or HBCD decreased API particle sizes, producing submicron-size particles. Surface morphology examination using scanning electron microscopy revealed API SDPs to be cylindrical and non-wrinkled. However, API-excipient SDPs were wrinkled and rough. Only HBCD SDPs were porous and non-aggregating, thereby suggesting superior aerodynamic properties and suitability for pulmonary delivery of these particles. HBCD formulations had the highest drug content in terms of both isoniazid (97.5%) and rifampicin (92.3%). Larger surface areas were obtained for SDPs of HBCD than those of other sugars. Regarding inhalational properties, HBCD formulations had higher emitted dose and fine-particle fractions than formulations of all other sugars tested. Our results confirm the feasibility of the formulation of hydrophilic and hydrophobic drug substances into a single-dosage preparation for pulmonary delivery using HBCD as an excipient.

Feasibility of highly branched cyclic dextrin as an excipient matrix in dry powder inhalers.

We investigated the feasibility of highly branched cyclic dextrin (HBCD) as an excipient matrix in dry powder inhalers (DPIs). The fine particles of HBCD and HBCD/active pharmaceutical ingredients (APIs) were prepared by spray-drying an ethanol-aqueous solution containing HBCD. The particle size of spray-dried HBCD itself was approximately 3.0µm with a wrinkled shape. Solid-state fluorescence emission spectroscopy of 1-naphthoic acid (1-NPA) showed that it was dispersed in a molecular dispersion/solid solution, if the model compound of 1-NPA was spray-dried with HBCD. Powder X-ray diffraction and differential scanning calorimetry indicate that 1-NPA was in the amorphous state after spray-drying with HBCD, which is confirmed by the fluorescence measurements, 1-NPA could be incorporated into HBCD. When the antimycobacterial agent, rifampicin, was spray-dried with HBCD for the purpose of pulmonary administration, the emitted dose and fine-particle fraction of the spray-dried particles of rifampicin with HBCD were 95.7±1.7% and 39.5±5.7%, respectively. The results indicated that HBCD possessed a high potential as an excipient in DPIs, not only by molecular association of API molecules with HBCD, but also by that of API fine crystals.