A Pan-Canadian Consensus Statement on First-Line PARP Inhibitor Maintenance for Advanced,High-Grade Serous and Endometrioid Tubal,Ovarian, and Primary Peritoneal Cancers

The majority of patients with advanced, high-grade epithelial-tubo ovarian cancer (EOC) respond well to initial treatment with platinum-based chemotherapy; however, up to 80% of patients will experience a recurrence. Poly(ADP-ribose) Polymerase (PARP) inhibitors have been established as a standard of care maintenance therapy to prolong remission and prevent relapse following a response to first-line platinum-chemotherapy. Olaparib and niraparib are the PARP inhibitors currently approved for use in the first-line maintenance setting in Canada. Selection of maintenance therapy requires consideration of patient and tumour factors, presence of germline and somatic mutations, expected drug toxicity profile, and treatment access. This paper discusses the current clinical evidence for first-line PARP inhibitor maintenance therapy in patients with advanced, high-grade EOC and presents consensus statements and a treatment algorithm to aid Canadian oncologists on the selection and use of PARP inhibitors within the Canadian EOC treatment landscape.     

Early carotid endarterectomy after acute stroke

PURPOSE: Carotid endarterectomy (CEA) after acute stroke is generally delayed 6 to 8 weeks because of fear of stroke progression. This delay can result in an interval stroke rate of 9% to 15%. We analyzed our results with CEA performed within 1 to 4 weeks of stroke. METHODS: Records for all patients undergoing CEA after stroke between 1980 and 2001 were analyzed. Perioperative evaluation included carotid duplex scanning or angiography, and head computed tomography or magnetic resonance imaging. All patients with nonworsening neurologic status, additional brain territory at risk for recurrent stroke, and severe ipsilateral carotid stenosis underwent CEA. Patients were grouped according to time of CEA after stroke: group 1, first week; group 2, second week; group 3, third week; group 4, fourth week. Statistical analysis was performed with the chi(2) test, logistic regression, and analysis of variance. RESULTS: Two hundred twenty-eight patients underwent CEA within 1 to 4 weeks of stroke. Perioperative permanent neurologic deficits occurred in 2.8% of patients in group 1 (72 procedures), 3.4% of patients in group 2 (59 procedures), 3.4% of patients in group 3 (29 procedures), and 2.6% of patients in group 4 (78 procedures). There was no relationship between location or size of preoperative infarct and time of surgery. Only preoperative infarct size correlated with probability of neurologic deficit after CEA (P <.05). CONCLUSION: Incidence of postoperative stroke exacerbation is similar at all intervals. The results are within acceptable limits for treatment of symptomatic carotid stenosis. CEA may be performed within 1 month of stroke with similar results at all intervals during this period.     

Effect of tidal volume and respiratory rate on the power of breathing calculation

BACKGROUND: The power of breathing (PoB) is used to estimate the mechanical workload of the respiratory system. Aim of this study was to investigate the effect of different tidal volume-respiratory rate combinations on the PoB when the elastic load is constant. In order to assure strict control of the experimental conditions, the PoB was calculated on an airway pressure-volume curve in mechanically ventilated patients. METHODS: Ten patients received three different tidal volume-respiratory rate combinations while minute ventilation was constant. Respiratory mechanics, PoB and its elastic and resistive components were calculated. Alternative methods to estimate the elastic workload were assessed: elastic work of breathing per litre per minute, elastic workload index (the square root of elastic work of breathing multiplied by respiratory rate) and elastic double product of the respiratory system (the elastic pressure multiplied by respiratory rate). RESULTS: Despite constant elastance and minute ventilation, the elastic PoB showed an increment greater than 200% from the lower to the greater tidal volume, accounting for approximately 80% of the whole PoB increment. On the contrary, elastic work of breathing per litre per minute, elastic workload index and elastic double product did not change. CONCLUSION: Changes in breathing pattern markedly affect the PoB despite constant mechanical load. Other indexes could assess the elastic workload without tidal volume dependence. Power of breathing use should be avoided to compare different mechanical loads or efficiencies of the respiratory muscles when tidal volume is variable.     

A preliminary study of PDA-based dietary self-monitoring in hemodialysis patients

OBJECTIVE: The purpose of this study was to pilot test an intervention to enhance the adherence of study participants to the hemodialysis dietary regimen. DESIGN: A single case study design was used to examine the potential effectiveness of the intervention over a 4-month period of time. SETTING: A dialysis center in southwestern Pennsylvania. PATIENTS: Of the five individuals entered into the study, one was male and four were female, four were black, and one was white. Participants were 63 to 70 years of age, and had been receiving dialysis for a median of 36 months (range, 18 to 84 months). INTERVENTION: The intervention included counseling to enhance self-efficacy, by a renal dietitian, paired with personal digital assistant-based dietary self-monitoring. Participants met twice per week with interventionists during the first 6 weeks, weekly during the second 6-week period, and biweekly in the final 4-week period. MAIN OUTCOME MEASURES: Monthly laboratory data regarding serum albumin, potassium, and phosphorus levels; Kt/V; and data on average monthly interdialytic weight gain were abstracted from the participants' medical records. C-reactive protein level was determined at baseline and at 4 months. RESULTS: Four of five study participants had an increase in serum albumin level from baseline to their final measurement, and one participant maintained a stable albumin level. Four of five participants also experienced a small increase in serum phosphorus level. Mixed results were obtained with regard to serum potassium and average monthly interdialytic weight gain. CONCLUSIONS: Because of the small sample and single case study design, caution must be used in drawing firm conclusions from this study. Data suggest that the intervention may result in improved dietary intake and improved serum albumin levels. With increased dietary intake, serum phosphorus levels may increase. Additional research is needed to determine the potential efficacy and cost-effectiveness of this intervention for improving dietary adherence.     

Impact of laryngeal mask airway and tracheal tube on pulmonary function during the early postoperative period

BACKGROUND: The tracheal tube (TT) produces reversible bronchoconstriction and increases pulmonary airway resistance compared to the laryngeal mask airway (LMA). The possible persistence of this effect in the postoperative period has not been studied. The aim of this study was to compare the early postoperative pulmonary function in healthy patients undergoing minor surgical procedures with the LMA or with the TT. METHODS: Sixty patients scheduled for saphenous vein stripping under general anaesthesia were randomised to receive the LMA or the TT. Before anaesthesia and 20 min after LMA or TT removal, pulse oxymetry values (SpO(2)) were recorded and patients performed forced spirometry in the supine position. RESULTS: Preoperative pulmonary function was normal in both groups. There were no differences between groups in the preoperative respiratory function test and SpO(2). Following surgery SpO(2), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) decreased in both groups. The FEV1/FVC did not change in either of the groups. In the TT group, compared to patients using the LMA, there was a greater relative decrease of SpO(2) (2.7 +/- 2.7% vs. 1.3 +/- 2.2%, P=0.017), FEV1 (17.6 +/- 12.2% vs. 8 +/- 17.4%, P=0.008), FVC (15.8 +/- 12.4% vs. 9 +/- 13.4%, P=0.023) and PEF (20.6% +/- 15.3% vs. 8.1 +/- 33.3%, P=0.033). CONCLUSIONS: This study demonstrates greater early postoperative respiratory restrictive syndrome and lower arterial oxygen saturation following tracheal intubation compared to LMA use in patients without respiratory disease.     

Lymphoproliferative disease of the orbit

PURPOSE OF REVIEW: Malignant lymphoma of the ocular adnexa has been reported on for many years, but many steps forward have been recently made. This paper highlights the staging strategies and treatment options based on a review of the most updated and relevant bibliography. RECENT FINDINGS: A relevant improvement in the management of ocular adnexal lymphoma is represented by PET, which improves the diagnosis and the staging of the disease. Acquisitions have been made in the treatment: low-dose radiotherapy is confirmed for primary orbital mucosa-associated lymphoid tissue lymphoma; oral chlorambucil is proposed as an alternative; immunotherapy is proposed for the treatment of systemic disease. Interestingly, the role of Chlamydia psittaci as the possible cause of mucosa-associated lymphoid tissue lymphomas and the efficacy of doxycycline for the treatment of ocular adnexal lymphomas have been investigated with promising results. A large series of natural killer/T-cell lymphoma has been described and its lethality despite aggressive conventional chemotherapy has been confirmed. SUMMARY: Orbital lymphoma is the most common malignant tumor of the orbit and its incidence is increasing proportionally with the rise of the average survival rate of the general population. The combined efforts of orbital surgeons, hematologists, oncologists and radiotherapists have lately produced a mass of new information that can effectively improve the management of orbital lymphoma.     

Deposition of autofluorescent eosinophil granules in pathologic bone marrow biopsies

Eosinophil granules are intensely autofluorescent when excited by green light. To determine if eosinophils degranulate in the bone marrows of patients with a variety of diseases, we used green light epifluorescence microscopy to examine deparaffinized and dezenkerized sections of 49 bone marrow core biopsies. In 14 of the biopsies, there was striking extracellular deposition of intensely autofluorescent eosinophil granules in addition to numerous intact eosinophils. Among the 14 specimens with extracellular autofluorescence were seven cases of leukemia, four cases of non-Hodgkin's lymphoma, two cases of myelofibrosis, and one case of pancytopenia with eosinophilia. In the remaining 35 specimens, only intact eosinophils were identifiable. There was no extracellular autofluorescence in three normal marrows, four marrows from AIDS patients, or three biopsies from patients with idiopathic thrombocytopenic purpura (ITP). We conclude that green light epifluorescence microscopy identifies extracellular deposits of eosinophil granules in bone marrow biopsies of some neoplastic disorders and in diseases associated with reticulin fibrosis.     

Atherosclerosis in light of the evidence from large statin trials

The results of the large trials with the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (or statins) in terms of clinical benefits in patients with coronary artery disease indicate that these drugs act in a complex way on several pathways involved in the atherosclerotic process. Beyond their lipid-lowering activity, statins appear to modify many characteristics of the arterial wall, resulting in protection against the progression of plaque growth and/or the precipitation of acute events. The so called "pleiotropic" effects of statins, such as the restoration of endothelial activity, the antioxidant potential or the antiproliferative effect on smooth muscle cells, have been investigated mainly in in vitro experiments. In the near future, it will be necessary to unravel the biological significance and the clinical relevance of these effects, which also involve other pathological conditions such as cancer and osteoporosis. Furthermore, lessons from the trials with statins have allowed a better understanding of the mechanisms leading to atherosclerosis which is now considered as an inflammatory process affecting the vascular wall. This has opened new perspectives in the search for the development of newer and more targeted anti-atherogenic drugs.