Real-World Palbociclib Use in HR+/HER2− Advanced Breast Cancer in Canada: The IRIS Study

Background: Palbociclib is a selective cyclin-dependent kinase (CDK) 4/6 inhibitor used in combination with aromatase inhibitors or fulvestrant for patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2)-negative advanced/metastatic breast cancer (ABC/MBC). Palbociclib was the first CDK 4/6 inhibitor approved for HR+/HER2− ABC/MBC treatment in Canada in combination with letrozole (P+L) as an initial endocrine-based therapy (approved March 2016), or with fulvestrant (P+F) following disease progression after prior endocrine therapy (approved May 2017). The Ibrance Real World Insights (IRIS) study ({"type":"clinical-trial","attrs":{"text":"NCT03159195","term_id":"NCT03159195"}}NCT03159195) collected real-world outcomes data for palbociclib-treated patients in several countries, including Canada. Methods: This retrospective chart review included women with HR+/HER2− ABC/MBC receiving P+L or P+F in Canada. Physicians reviewed medical records for up to 14 patients, abstracting demographic and clinical characteristics, treatment patterns, and clinical outcomes. Progression-free rates (PFRs) and survival rates (SRs) at 6, 12, 18, and 24 months were estimated via Kaplan–Meier analysis. Results: Thirty-three physicians examined medical records for 247 patients (P+L, n = 214; P+F, n = 33). Median follow-up was 8.8 months for P+L and 7.0 months for P+F. Most patients were initiated on palbociclib 125 mg/d (P+L, 90.2%; P+F, 84.8%). Doses were reduced in 16.6% of P+L and 14.3% of P+F patients initiating palbociclib at 125 mg/d. The PFR for P+L was 90.3% at 12 months and 78.2% at 18 months; corresponding SRs were 95.6% and 93.0%. For P+F, 6-month PFR was 91.0%; 12-month SR was 100.0%. Conclusions: Dose reduction rates were low and PFR and SR were high in this Canadian real-world assessment of P+L and P+F treatments, suggesting that palbociclib combinations are well tolerated and effective.     

Pediatric intracranial aneurysms—clinical characteristics and outcome of surgical treatment

Object Intracranial aneurysms are rare in children and have different epidemiological, clinical, and morphological characteristics and outcome from those in adults. Materials and methods We analyzed demographic, clinical, radiologic features, treatment, and outcome in 55 patients <18 years of age, treated from Jan 1995 through December 2005. Results Intracranial aneurysms in children below 18 years constituted 4% of all intracranial aneurysms. Internal Carotid artery (ICA) bifurcation was the commonest location. About half of the aneurysms were complex. Three-fourth of the patients required surgical treatment. Two patients died, constituting 5% mortality. Two patients (5%) had poor outcome, whereas the majority (90%) had a favorable outcome. Conclusions Pediatric aneurysms have male predominance, higher incidence of clinical features of mass effect or seizures, high incidence of large, traumatic/mycotic aneurysms, associated illnesses and ICH/IVH and hydrocephalus, better Hunt and Hess grades at presentation, ICA bifurcation as the commonest site, and better outcome than their adult counterparts.     

Primary hydatid cyst of the breast: A case report

We describe herein the rare case of a hydatid cyst found in the breast of a 26-year-old woman. Clinically, the mass was at first suspected of being a fibroadenoma, but fine needle aspiration cytology (FNAC) yielded clear fluid only. Histopathologic examination of the resected speciman confirmed that it was a hydatid cyst.     

Parotid gland leiomyosarcoma in a child: an extremely unusual neoplasm.

We report the case of an 8-year-old boy with a parotid mass diagnosed to be a leiomyosarcoma. Considering the unresectable extent of the mass, the patient was subjected to radiotherapy. The patient developed distant metastasis following the course of radiotherapy and was put on chemotherapy. The child was lost to further follow up. To our knowledge, this is the first reported case in the English-language literature of such an entity in the pediatric age group.     

Psychiatric considerations in pulmonary disease.

Lung disease is a prominent cause of morbidity and mortality worldwide. When a patient has a common lung disease, such as asthma, or a less prevalent one, such as idiopathic pulmonary fibrosis, psychiatric issues should be considered as an integral part of the care plan for each patient. There have been many studies of psychologic factors and psychiatric syndromes in various lung diseases and their treatment. In this article, the authors focus on an evidence-based approach to reviewing this clinical literature.     

Protection Against Chemically-Induced Oxidative Gastrointestinal Tissue Injury in Rats by Bismuth Salts

Oxygen free radicals (OFR) are implicated in thepathogenesis of stress, chemically induced gastriclesions, and gastrointestinal injury. Theconcentration-dependent scavenging abilities of bismuthsubsalicylate (SBS), colloidal bismuth subcitrate (CBS), andselected OFR scavengers, including superoxide dismutase(SOD), catalase, mannitol, and allopurinol were examinedagainst biochemically or chemically generated superoxide anion, hydroxyl radical, andhypochlorite radical plus hypochlorous acid based on achemiluminescence assay. Furthermore, both gastric (GM)and intestinal mucosa (IM) were individually exposed in vitro to these free radical generatingsystems, and the concentration-dependent protectiveabilities of SBS and CBS against lipid peroxidation (LP)were compared with selected OFR scavengers. In addition, 24-hr fasted rats were orally treated with thenecrotizing agents 0.6 M HCl, 0.2 M NaOH, 80% ethanol,and aspirin (200 mg/kg). The extent of tissue injury inthe GM and IM was determined by assessing LP, DNA fragmentation, and membrane microviscosity.Dose- and time-dependent in vivo protective abilities ofCBS (100 mg/kg) and SBS (15 mg/kg) were also assessed.Following incubations with superoxide anion and hydroxyl radical generating systems in thepresence of 125 mg SBS/liter, approximately 47% and 61%inhibitions were observed in the chemiluminescenceresponse, respectively, while 48% and 46% inhibitions were observed with 125 mg CBS/liter. SBS andCBS exerted similar abilities towards hypochloriteradical plus hypochlorous acid. Approx. 3.1- and3.7-fold increases in LP were observed in the GM and IMof rats following oral administration of 0.6 MHCl. Pretreatment of the rats with SBS and CBS decreased0.6 M HCl-induced LP in the GM by approx. 39% and 27%,respectively, with similar decreases in LP in the IM. SBS exhibited better protectiveabilities towards 0.6 M HCl and 0.2 m NaOH-induced GMand IM injury as compared to CBS. SBS and CBS providedsimilar protection towards 80% ethanol-induced gastric injury, while CBS exerted a superior protectiveability towards aspirin-induced gastric injury. Theresults demonstrate that both SBS and CBS can scavengereactive oxygen species and prevent tissue damage produced by OFR.     

Synthesis,Physicochemical Properties,and Cytotoxicity of a Series of 5′-Ester Prodrugs of 5-Iodo-2′-deoxyuridine

Five aliphatic 5-esters of 5-iodo-2deoxyuridine (IDU) were synthesized via an acid chloride alcoholysis reaction. The solubility in pH 7.4 phosphate buffer, lipophilicity as determined by partition experiments in octanol/pH 7.4 buffer, and cytotoxicity of these potential prodrugs were evaluated. The esters showed a 43- to 250-fold increase in lipophilicity and a 1.6- to 14-fold decrease in aqueous solubility relative to IDU. At a concentration of 50 µM, all esters showed reduced cytotoxicity toward uninfected Vero cells relative to IDU.