Extrapleural pneumonectomy with adjuvant therapy is appropriate treatment for selected patients with malignant mesothelioma selected using a revised staging system.
Extracorporeal membrane oxygenation (ECMO) for severe respiratory failure can be used to maintain adequate gas exchange but precludes ambulation and may lead to further deconditioning. We present a case of ambulatory ECMO for severe respiratory failure using a dual-lumen single cannula system.
CLINICAL SUMMARYA 49-year-old man with chronic carbon dioxide retention and elevated serum bicarbonate levels awaiting lung transplantation for severe chronic obstructive pulmonary disease (COPD) had respiratory failure owing to an acute COPD exacerbation. He was admitted to the medical intensive care unit and began receiving mechanical ventilation. Arterial blood gas analysis on admission demonstrated a PO 2 of 62 mm Hg and a PCO 2 greater than 100 mm Hg. Despite aggressive treatment with steroids, inhaled bronchodilators, antibiotics, sildenafil, inhaled nitric oxide, and theophylline for 2 weeks, the patient remained ventilator dependent. He was therefore advanced to ambulatory ECMO to alleviate the need for mechanical ventilation and allow aggressive rehabilitation.Under general anesthesia in the cardiac operating theater, the internal jugular vein was located with ultrasound and marked. A small incision was made over the vein and dissection was carried down to the internal jugular vein. To allow a more comfortable lie of the proximal dual-lumen catheter FIGURE 1. Insertion of the dual-lumen cannula into the internal jugular vein by tunneling from the right subclavicular chest. Note the subtle curve of the tunneled cannula. Inflow to the ECMO circuit is from the tip of the cannula located in the inferior vena cava and fenestrations in the mid-cannula at the superior vena cava-right atrial junction. Outflow between these 2 points is directed at the tricuspid valve.
Improvements in the durability of membrane blood oxygenators and pumps have prompted renewed consideration of extracorporeal membrane oxygenation in patients with severe lung disease. This report describes an attempt to augment extracorporeal membrane oxygenation with the goal of ambulation by minimizing mechanical ventilatory support and using aggressive in-and-out-of-bed rehabilitation.
Severe adult respiratory distress syndrome (ARDS) is associated with failure to maintain adequate gas exchange. There is increasing success using extracorporeal membrane oxygenation (ECMO) for respiratory failure; the longest reported surviving patient has been supported by ECMO for 57 days. At best about 50% wean from ECMO and should weaning fail their course is fatal. ECMO is generally considered to be a contraindication for successful lung transplantation. This report describes a patient maintained on ECMO for 107 days who underwent bilateral lung transplantation and weaned from organ-perfusion support. He survived for 351 days post-transplantation and died from Pseudomonas aeruginosa pneumonia. ECMO can be used for prolonged intervals to support patients with severe ARDS without complications that preclude lung transplantation. As ECMO use becomes more frequent, it becomes critical to determine criteria that would optimise patient selection for transplantation from ECMO.
Procurement of a facial vascularized composite allograft (VCA) should allow concurrent procurement of all solid organs and ensure their integrity. Because full facial procurement is time–intensive, “simultaneous–start” procurement could entail VCA ischemia over 12 h. We procured a total face osteomyocutaneous VCA from a brain–dead donor. Bedside tracheostomy and facial mask impression were performed preoperative day 1. Solid organ recovery included heart, lungs, liver, kidneys, and pancreas. Facial dissection time was 12 h over 15 h to diminish ischemia while awaiting recipient preparation. Solid organ recovery began at 13.5 h, during midfacial osteotomies, and concluded immediately after facial explantation. Facial thoracic and abdominal teams worked concurrently. Estimated blood loss was 1300 mL, requiring five units of pRBC and two units FFP. Urine output, MAP, pH and PaO2 remained normal. All organs had good postoperative function. We propose an algorithm that allows “face first, concurrent completion” recovery of a complex facial VCA by planning multiple pathways to expedient recovery of vital organs in the event of clinical instability. Beginning the recipient operation earlier may reduce waiting time due to extensive recipient scarring causing difficult dissection.
HIV drug resistance continues to
emerge; consequently, there is
an urgent need to develop next generation antiretroviral therapeutics.1 Here we report on the structural and kinetic
effects of an HIV protease drug resistant variant with the double
mutations Gly48Thr and Leu89Met (PRG48T/L89M), without
the stabilizing mutations Gln7Lys, Leu33Ile, and Leu63Ile. Kinetic
analyses reveal that PRG48T/L89M and PRWT share
nearly identical Michaelis–Menten parameters; however, PRG48T/L89M exhibits weaker binding for IDV (41-fold), SQV (18-fold),
APV (15-fold), and NFV (9-fold) relative to PRWT. A 1.9
Å resolution crystal structure was solved for PRG48T/L89M bound with saquinavir (PRG48T/L89M-SQV) and compared
to the crystal structure of PRWT bound with saquinavir
(PRWT-SQV). PRG48T/L89M-SQV has
an enlarged active site resulting in the loss of a hydrogen bond in
the S3 subsite from Gly48 to P3 of SQV, as well as less favorable
hydrophobic packing interactions between P1 Phe of SQV and the S1
subsite. PRG48T/L89M-SQV assumes a more open conformation
relative to PRWT-SQV, as illustrated by the downward
displacement of the fulcrum and elbows and weaker interatomic flap
interactions. We also show that the Leu89Met mutation disrupts the
hydrophobic sliding mechanism by causing a redistribution of van der
Waals interactions in the hydrophobic core in PRG48T/L89M-SQV. Our mechanism for PRG48T/L89M-SQV drug resistance
proposes that a defective hydrophobic sliding mechanism results in
modified conformational dynamics of the protease. As a consequence,
the protease is unable to achieve a fully closed conformation that
results in an expanded active site and weaker inhibitor binding.
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