In-vivo EPID dosimetry for IMRT and VMAT based on through-air predicted portal dose algorithm.

We have adapted the methodology of Berry et al. (2012) for Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) treatments at a fixed source to imager distance (SID) based on the manufacturer's through-air portal dose image prediction algorithm. In order to fix the SID a correction factor was introduced to account for the change in air gap between patient and imager. Commissioning data, collected with multiple field sizes, solid water thicknesses and air gaps, were acquired at 150 cm SID on the Varian aS1200 EPID. The method was verified using six IMRT and seven VMAT plans on up to three different phantoms. The method's sensitivity and accuracy were investigated by introducing errors. A global 3%/3 mm gamma was used to assess the differences between the predicted and measured portal dose images. The effect of a varying air gap on EPID signal was found to be significant - varying by up to 30% with field size, phantom thickness, and air gap. All IMRT plans passed the 3%/3 mm gamma criteria by more than 95% on the three phantoms. 23 of 24 arcs from the VMAT plans passed the 3%/3 mm gamma criteria by more than 95%. This method was found to be sensitive to a range of potential errors. The presented approach provides fast and accurate in-vivo EPID dosimetry for IMRT and VMAT treatments and can potentially replace many pre-treatment verifications.

Synthesis of LJP 993, a multivalent conjugate of the N-terminal domain of beta2GPI and suppression of an anti-beta2GPI immune response.

LJP 993, a tetravalent conjugate of the amino-terminal domain (domain 1) of beta2GPI, was synthesized, and studies were carried out to explore the ability of LJP 993 to bind anti-beta2GPI antibodies and to function as a B cell toleragen. Domain 1 was expressed in Pichia pastoris, and the N-terminus was site-specifically modified by a transamination reaction converting the N-terminal glycine to a glyoxyl group. A tetravalent platform was synthesized with linkers that terminate in aminooxy groups. This was accomplished by preparing an ethylene glycol-based heterobifunctional linker that contains both a Boc-protected aminooxy group and a free primary amine. The linker was used to modify a tetravalent platform molecule by reacting the amino groups on the linker with 4-nitrophenyl carbonate esters on the platform to provide a linker-modified platform, and the Boc protecting groups were removed to provide a tetravalent aminooxy platform. Glyoxylated domain 1 was attached to the platform to provide LJP 993 by formation of oxime bonds. The protein domains of LJP 993 retain activity as evidenced by the ability of LJP 993 to bind to anti-beta2GPI antibodies. Dissociation constants (Kd) for domain 1 and LJP 993 bound to immobilized affinity-purified anti-beta2GPI antibodies from autoimmune thrombosis patients were determined using surface plasmon resonance. An immunized mouse model was developed to test the ability of LJP 993 to act as a toleragen. A thiol containing domain 1 analogue was expressed in insect cells using the baculovirus expression system, and it was used to prepare an immunogenic conjugate of domain 1 and maleimide-derivatized keyhole limpet hemocyanin (KLH). Mice were immunized with the KLH conjugate, and spleen cells were harvested from the immunized mice. The cells were incubated with various concentrations of LJP 993 and transferred to mice whose immune systems had been compromised by irradiation. The hosts were then boosted with the KLH-domain 1 conjugate, and after 7 days their antibody levels were measured. Host mice receiving cells that were treated with LJP 993 produced significantly lower amounts of anti-domain 1 antibodies than controls which received untreated cells, indicative of B cell tolerance.

Use of Toronto stentless porcine valve in patients with aortic dilation.

One of the contraindications for a stentless aortic valve is dilation of the aorta such that the sinotubular ridge is more than 2 mm larger than the annulus. Since May of 1994, 134 patients have had their aortic valve replaced with St Jude Toronto SPV valves; of these, 38 patients have required sinotubular ridge reduction. This was done by using one or more pleats in the aorta between the commisural posts. There were 20 patients with one pleat, 12 patients with two pleats, 5 patients with three pleats, and 1 patient with four pleats. In addition, three Toronto SPV valves were used in patients with significant calcification in the native coronary sinuses. All of the valves have had trace or no aortic insufficiency and have not developed aortic insufficiency in follow-up evaluation. Mean gradients remain low (<10 mm Hg). These valves have been much more versatile than originally expected and can be used in patients with mild to moderate aortic dilation and calcification.

A positive approach to chemotherapy.

This article deals with the care of patients receiving chemotherapy for breast cancer. Using a case study, it highlights the importance of supporting patients and helping them to cope with their fears and anxieties about the treatment and its possible side-effects by considering not only their physical but also their psychological needs.

Pulmonary mucormycosis: results of medical and surgical therapy.

Mucormycosis is an opportunistic fungal infection that commonly begins by invading the respiratory tract. The purpose of the present study was to define the clinical presentation of pulmonary mucormycosis and to evaluate current treatment regimens. Thirty patients treated at our institution and 225 cases reported in the literature were reviewed. For the combined groups, the mean age at presentation was 41 +/- 21 years and associated medical conditions included leukemia or lymphoma (37%), diabetes mellitus (32%), chronic renal failure (18%), history of organ transplantation (7.6%), or a known solid tumor (5.6%). The in-hospital mortality was 65% for patients with isolated pulmonary mucormycosis, 96% for those with disseminated disease, and 80% overall. The mortality in patients treated surgically was 11%, significantly lower than the 68% mortality in those treated medically (p = 0.0004). The most common causes of death were fungal sepsis (42%), respiratory insufficiency (27%), and hemoptysis (13%). Pulmonary mucormycosis has a high mortality; however, antifungal agents appear to improve survival. In addition, surgical resection may provide additional benefit to patients with pulmonary mucormycosis confined to one lung.

Pulsatile versus nonpulsatile reperfusion improves cerebral blood flow after cardiac arrest.

Cardiopulmonary bypass using nonpulsatile flow (NF) is currently advocated for treating refractory cardiac arrest. Although the heart can be revived using cardiopulmonary bypass support, the brain must recover if such therapy is to be considered successful. Previous studies have demonstrated that pulsatile flow (PF) reperfusion can improve neurologic outcome compared with NF reperfusion after cardiac arrest. The purpose of this study was to assess cerebral perfusion and oxygen consumption during either PF or NF reperfusion after cardiac arrest. Dogs (n = 22) underwent a 15-minute cardiac arrest followed by 1 hour of either PF or NF reperfusion. Microsphere techniques were used to assess cerebral perfusion and oxygen consumption at 3, 15, and 60 minutes of reperfusion. Mean arteriovenous gradients and total brain flows were similar in both groups. However, cerebral oxygen consumption was significantly improved at 3 minutes of reperfusion with PF versus NF (1.8 +/- 0.3 versus 0.9 +/- 0.3 mL O2.dL-1.min-1, respectively; p < 0.05). These results were coincident with improved gray-to-white flow ratios at 3 minutes of PF versus NF reperfusion (5.2 +/- 1.0 versus 2.0 +/- 0.3, respectively; p < 0.05). There were no statistically significant differences in brain perfusion variables by 15 minutes of reperfusion. However, a relative hyperemia was exhibited at 15 minutes of NF versus PF reperfusion, which suggests nutrient flow was insufficient during early NF versus PF reperfusion. In conclusion, PF reperfusion can better restore cerebral blood flow and oxygen consumption than can NF reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensing lead insulation fractures following implantable cardioverter-defibrillator placement.

The insulation of implantable cardioverter-defibrillator (ICD) sensing leads can fracture, causing device malfunction. Before March 1989, 32 patients received silicon CPI K54 sensing leads. Of these, four (12.5%) experienced discharges while in sinus rhythm. Subsequent ICD interrogation revealed that abdominal muscular contraction triggered discharges in two patients, but no abnormal sensing could be elicited in the other two patients. These patients subsequently were found to have sensing lead fractures. All sensing leads appeared intact radiographically but at reoperation were found to have insulation fractures 2-4 cm from the pin. The mechanism of fracture appears to be related to chronic intermittent lead compression between the anterior abdominal wall musculature and the ICD generator. Since March 1989, 134 patients have undergone ICD implantation with improved CPI 4312 sensing leads; none of these patients has experienced sensing lead fractures. The insulation of these leads is 2.5 times thicker than the K54 (1.0 mm vs. 0.4 mm). Patients with K54 sensing leads are at an increased risk for sensing lead insulation fracture and merit close surveillance. More importantly, sensing lead fractures must be considered in patients who present with inappropriate ICD discharges.

Current morbidity, mortality, and survival after bronchoplastic procedures for malignancy.

The number of patients reported to have undergone bronchoplastic procedures has increased nearly fourfold in the past decade. These techniques represent excellent surgical therapy for patients with benign endobronchial lesions, traumatic airway disruptions, or tumors of low-grade malignant potential, and for select patients with surgically resectable lung cancer. Eighty-nine percent of bronchoplastic procedures are performed for malignancy. We reviewed 1,915 bronchoplastic procedures for carcinoma reported over the past 12 years to determine the incidence of complications and survival. Complications included local recurrence (10.3%), 30-day mortality (7.5%), pneumonia (6.7%), atelectasis (5.4%), benign stricture or stenosis (5.0%), bronchopleural fistulas (3.5%), empyema (2.8%), bronchovascular fistulas (2.6%), and pulmonary embolism (1.9%). Results were further stratified into sleeve lobectomy and sleeve pneumonectomy groups. Five-year survivals for stage I, II, and III carcinoma were 63%, 37%, and 21%, respectively. Sleeve lobectomy for carcinoma extends surgical therapy to select patients with complication rates comparable to pneumonectomy and long-term survival similar to that for conventional resections.

Intraoperative timing may provide criteria for use of post-cardiotomy ventricular assist devices.

When surgeons consider ventricular assist devices (VADs) for post-cardiotomy support, unnecessary delays and early use can have detrimental effects on patient outcome. The authors analyzed the timing of intraoperative events in all patients receiving post-cardiotomy VAD support at their institution during a 2-1/2 year period (N = 17). They used ability to wean patients from VAD support as a measure of outcome. Neither preoperative risk factors nor the timing of distinct intraoperative events (e.g., cross-clamp time, total bypass time, delay to VAD) significantly differed between those patients able (Group I, n = 9) and those unable (Group II, n = 8) to be weaned from VAD support. The authors did find, however, that the time intervals from completion of the cardiac procedure to insertion of either an intra-aortic balloon pump (time to IABP) or VAD (time to VAD) were predictive of outcome when normalized to the duration of the cardiac procedure (DCP). [Time to IABP]/DCP ratios of < 1.0 versus > 1.0 (p = 0.02) and [time to VAD]/DCP ratios of < 2.5 versus > 2.5 (p = 0.10) each segregated Group I and II patients, respectively. Appropriate timing criteria for VAD insertion may be predicted during surgery by consideration of the duration of the cardiac procedure. This approach may attenuate tendencies to delay VAD use without leading to premature VAD insertion in the post-cardiotomy setting.

Prophylactic implantable defibrillator patches in patients at high risk for malignant ventricular dysrhythmias.

The indications for prophylactically placing implantable cardioverter defibrillator (ICD) patches at cardiac surgery are unclear. Over the past 4 years, 25 patients have undergone placement of prophylactic ICD patches at the authors' institution. Indications were severe coronary artery disease with ventricular tachycardia (VT) (n = 14) or ventricular fibrillation (VF) (n = 2), and left ventricular aneurysmectomy and/or subendocardial resection (SER) (n = 9). Four patients died in-hospital, three from refractory VT (which could be transthoracically cardioverted until recurrence was unremitting), and one from congestive heart failure (CHF). All of the remaining 21 patients underwent post-operative electrophysiologic studies (EPS), and 12 had inducible VT (8/14 CABG, 4/7 SER). Eight of the 12 inducible patients had generators implanted, whereas 3 patients were controlled medically. One patient refused generator implantation and died at home from sudden cardiac death, and one initially non-inducible patient required late ICD generator placement, yielding a total of nine patients who received generators. All nine of these patients are currently alive at 14 +/- 7 months follow-up, and five have subsequently received appropriate ICD discharges. In patients undergoing cardiac surgery considered preoperatively or intraoperatively to be at increased risk for VT/VF and too unstable for preoperative EPS, prophylactic ICD patches should be considered.

Cardiac pathology following resuscitative circulatory support. Direct mechanical ventricular actuation versus cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is currently advocated for treating refractory cardiac arrest. Direct Mechanical Ventricular Actuation (DMVA) is an alternative method that does not contact the blood and has other unique advantages for providing resuscitative circulatory support, including rapid application and relative technical simplicity. The purpose of this study was to assess pathologic changes in the heart following resuscitation with either CPB or DMVA. Dogs (n = 22) received 1 hr of CPB (n = 11) or DMVA (n = 11) following a 12.5 min cardiac arrest. All deaths [4/11 (CPB) vs. 2/11 (DMVA), p = 0.31] occurred during the initial 24 postoperative hours. At 7 days, survivors had magnetic resonance imaging to determine cardiac ejection fraction [46% (CPB) vs. 51% (DMVA), p = 0.39], as well as the presence of cardiac wall motion abnormalities [50% (CPB) vs. 33% (DMVA), p = 0.57] and gross cardiac lesions [17% (CPB) vs. 17% (DMVA)]. The survivor's hearts were then extirpated, fixed, and examined for gross lesions [2/7 (CPB) vs. 0/9 (DMVA), p = 0.17]. Transmural sections of the anterior and posterior papillary muscles were histologically evaluated. The severity and extent of epicardial fibrosis and focal myocyte necrosis did not differ between groups. These data demonstrate that DMVA does not cause more myocardial trauma than CPB when used to provide resuscitative circulatory support. Therefore, the unique attributes of DMVA may improve resuscitation outcome in patients who suffer refractory cardiac arrest, without additional risk of cardiac injury.

Pulsatile reperfusion after cardiac arrest improves neurologic outcome.

Cardiopulmonary bypass (CPB) using nonpulsatile flow (NPF) is advocated for refractory cardiac arrest. This study examined cerebral outcome after resuscitation with pulsatile flow (PF) versus NPF. Dogs arrested for 12.5 minute were reperfused with NPF (n = 11) using roller pump CPB or PF (n = 11) using mechanical biventricular cardiac massage. Pump flows were similar between groups; however early arterial pressures were greater during PF versus NPF, *p less than 0.05. Circulatory support was weaned at 60 minutes' reperfusion. Neurologic recovery of survivors (n = 16) was significantly better after PF versus NPF, *p = 0.01. The presence of brain lesions on magnetic resonance images did not significantly differ between groups at 7 days. Brain then were removed and regions examined for ischemic changes. Loss of CA1 pyramidal neurons was more severe after NPF versus PF, +p = 0.009. Ischemic changes were more frequent after NPF in the caudate nucleus (+p = 0.009) and watershed regions of the cerebral cortex (+p = 0.062), compared with PF. These results demonstrate that PF improves cerebral resuscitation when treating cardiac arrest with mechanical circulatory support (* = MANOVA with repeated measures, + = categorical data analysis.

Myocardial tolerance to ischemia after resuscitation. Direct mechanical ventricular actuation versus cardiopulmonary bypass.

This study assessed myocardial ischemia after resuscitation from cardiac arrest using direct mechanical ventricular actuation (DMVA) or cardiopulmonary bypass (CPB). Myocardial ischemic tolerance was better after DMVA resuscitation. Resuscitation using DMVA, when compared with CPB, may improve outcome when subsequent coronary artery bypass grafting (CABG) is required.