Chronic cough is a common chief complaint in ambulatory clinics. Unlike most cases that are caused by upper airway cough syndrome, gastroesophageal reflux disease, asthma, and non-asthmatic eosinophilic bronchitis, chronic cough can also be the presenting feature of a Chiari malformation. Our case is that of a 39-year-old female who had a chronic cough associated with shortness of breath, and when severe, associated with loss of consciousness. Her cough was refractory to conventional management. Further workup including pulmonary functions tests (PFT), laryngoscopy, high-resolution CT of the chest, an upper GI series, and esophageal pH manometry study were all normal. An MRI of her brain was obtained due to her syncopal episodes and revealed findings concerning a type 1 Chiari malformation. She subsequently underwent a Chiari decompression with patchy duraplasty and tonsilloplasty with cervical vertebrae 1 and 2 (C1-C2) laminectomy with a resolution of her symptoms. Chiari malformations are sometimes inherited but are often sporadic in nature, and, thus, appropriate diagnosis is key. Our patient is unique in that she presented at an older age, suggesting that atypical etiologies of a chronic cough refractory to conventional treatments must be considered.
Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients.
e20013 Background: Autologous stem cell transplantation (ASCT) has improved long-term survival for many patients with multiple myeloma (MM), but not all patients respond to ASCT favorably, and many experience disease relapse. Our goal was to explore various disease parameters in patients with MM that might be associated with adverse outcomes after receiving ASCT. Methods: We performed a retrospective medical record review of adult patients with MM who underwent ASCT at Henry Ford Hospital between January 1, 2010 and November 1, 2020. Age, sex, international staging system stage, type of induction therapy, bone marrow cytogenetics and/or fluorescence in situ hybridization, International Myeloma Working Group (IMWG) treatment response criteria categories before ASCT, and the use of maintenance therapy were collected. Outcomes analyzed were time to relapse (TTR) and overall survival (OS). Cox regression analysis was performed. Results: A total of 321 patient records were analyzed: 194 (60.4%) patients were < 65 years old; 185 (57.6%) were men; 162 (50.5%) were Black, and 140 (43.6%) were White. IMWG treatment response categories before ASCT included 250 (78.2%) patients with partial response (PR) and very good partial response (VGPR) combined, and 40 (12.5%) with complete response (CR). There were 69 (21.4 %) patients classified with high-risk cytogenetics. Commonly used induction therapies included 96 (29.9%) patients receiving bortezomib/lenalidomide/dexamethasone, 21 patients (9%) receiving lenalidomide/dexamethasone, 80 patients (24.9%) receiving bortezomib/dexamethasone, and 30 patients (9.3%) receiving cyclophosphamide/bortezomib/dexamethasone, while other patients received a combination of other induction therapies. Mean time from ASCT and last follow-up date was 3.94 years. The overall mean TTR was 29.4 months and OS was 44.8 months. Univariate analysis showed that pre-ASCT treatment response status of combined PR/VGPR was associated with higher hazard of dying than CR (hazard ratio 3.03; 95% CI, 1.23-7.46); however, multivariate analysis showed that PR/VGPR status before ASCT was not significantly associated with increased TTR compared to CR (hazard ratio 1.29; CI, 0.65-2.59). Patients with pre ASCT CR status had longer OS than those with PR/VGPR status (hazard ratio 2.75; CI, 0.995-7.61; p < 0.05). No other variables, including cytogenetic risk were associated with a difference in OS or TTR. Conclusions: Being at CR status before receiving ASCT may indicate a reduced risk of death in MM patients compared to PR and VGPR status, regardless of upfront therapies. Since multiple factors, including treatment type, impact CR status in patients with MM, we believe that studying evolving risk-adapted front-line therapies will help guide optimized treatment strategies to improve overall survival.
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