Diabetic Ketoacidosis and Profound Insulin Resistance From Brentuximab Vedotin.

Hodgkin's lymphoma is commonly treated with a combination of chemotherapy drugs including doxorubicin, bleomycin, vinblastine, and dacarbazine. Antibody-drug conjugates such as brentuximab vedotin are now being used to treat Hodgkin's lymphoma that has not responded to standard treatment. Brentuximab vedotin is a monoclonal antibody that selectively delivers a cytotoxic agent, monomethyl auristatin E, which targets cells expressing surface CD30 markers, a protein that may be found in high amounts in some cancer cells including lymphoma cells. Common adverse effects of the drug include diarrhea, nausea, anemia, and fatigue. We present a case of a patient with diabetic ketoacidosis and profound insulin resistance secondary to brentuximab. Diabetic ketoacidosis is a rare but serious adverse reaction in this growing class of antibody-drug conjugates.

A simple test-based frailty index to predict survival among cancer patients with an unplanned hospitalization: An observational cohort study.

BACKGROUND: Frailty is a state of increased vulnerability to stressors, and predicts risk of adverse outcomes, such as mortality. Frailty can be defined by a frailty index (FI) using an accumulation of deficits approach. An FI comprised of 20 items derived from our previously studied test-based frailty index (TBFI) and an additional 33 survey-based elements sourced from the standard CGA was developed to evaluate if predictive validity of survival was improved. METHODS: One hundred eighty-nine cancer patients during acute hospitalization were consented between September 2018 and May 2019. Frailty scores were calculated, and patients were categorized into four groups: non-frail (0-0.2), mildly frail (0.2-0.3), moderately frail (0.3-0.4), and severely frail (>0.4). Patients were followed for 1-year to assess FI and TBFI prediction of survival. Area under the curve (AUC) statistics from ROC analyses were compared for the FI versus TBFI. RESULTS: Increasing frailty was similarly associated with increased risk of mortality (HR, 4.5 [95% CI, 2.519-8.075] and HR, 4.1 [95%CI, 1.692-9.942]) and the likelihood of death at 6 months was about 11-fold (odds ratio, 10.9 [95% CI, 3.97-33.24]) and 9.73-fold (95% CI, 2.85-38.50) higher for severely frail patients compared to non-frail patients for FI and TBFI, respectively. This association was independent of age and type of cancer. The FI and TBFI were predictive of survival for older and younger cancer patients with no significant differences between models in discriminating survival (FI AUC, 0.747 [95% CI, 0.6772-0.8157] and TBFI AUC, 0.724 [95% CI, 0.6513-0.7957]). CONCLUSIONS: The TBFI was predictive of survival, and the addition of an in-person assessment (FI) did not greatly improve predictive validity. Increasing frailty, as measured by a TBFI, resulted in a meaningfully increased risk of mortality and may be well-suited for screening of hospitalized cancer patients.

Diffuse Intrasinusoidal Hepatic Metastasis from Breast Cancer Presenting as Liver Failure: Effective and Rapid Treatment with Weekly Low-Dose Adriamycin.

BACKGROUND Hepatic metastasis is well known in breast cancer. Approximately 12-20% of breast cancer patients will develop liver metastasis, which usually presents as discrete mass lesions. Rarely, metastatic spread can be so diffuse that it is unidentifiable on imaging but can progress to fulminant hepatic failure. Our case report suggests that clinicians need to have a high index of suspicion when patients present with rapidly decompensating liver failure in the absence of discrete radiologic hepatic lesions, and that weekly Adriamycin should be considered as a first-line therapeutic option. CASE REPORT A 28-year-old African American woman with a history of locally advanced estrogen receptor-positive, progesterone receptor-negative, and HER2-negative breast cancer presented with right upper quadrant abdominal pain and bilateral lower extremity swelling. She had been treated 3 years prior with neoadjuvant Adriamycin/cyclophosphamide - Taxol, bilateral mastectomies, radiation therapy, and tamoxifen. Diagnostic imaging revealed massive hepatomegaly and extensive areas of liver ischemia/necrosis without discrete masses or arterial/venous thrombosis. Biopsy of the liver revealed metastatic carcinoma diffusely infiltrating the hepatic sinusoids. Extensive work up for other etiologies of liver disease was negative. The patient's liver function quickly decompensated over several days. She was treated with weekly single-agent low-dose Adriamycin, and this resulted in successful reversal of her liver function tests back to baseline. CONCLUSIONS In addition to having a high index of suspicion for diffuse intrasinusoidal hepatic metastasis, physicians should consider weekly low-dose Adriamycin as a first-line therapeutic option for patients with progressive liver failure and biopsy-confirmed metastatic carcinoma diffusely infiltrating the hepatic sinusoids.

Flexural Exanthema From Enfortumab Vedotin.

Urothelial malignancies are commonly treated with platinum-based therapies. Newer trials have tested antimitotic therapies such as enfortumab vedotin as viable treatment therapy for refractory malignany. Enfortumab vedotin targets nectin-4, a member of a family of calcium-dependent, immunoglobulin-like adhesion molecules found in adherens junctions and expressed in various epithelial malignancies, including bladder, breast, lung, ovarian, head/neck, and esophageal cancers. We present a case of a patient with symmetrical drug-related intertriginous and flexural exanthema secondary to enfortumab. He was successfully treated with topical corticosteroids. Cutaneous toxicity appears to be a common adverse reaction in this growing class of antibody-drug conjugates.

Lymphocele Containing Staphylococcus lugdunensis.

Staphylococcus species are a leading cause of community-acquired bacteremia. Of them, the most serious cause of mortality is from methicillin-resistant Staphylococcus aureus, with mortality rates as high as 40%. Another Staphylococcus species that has been noted to cause equal levels of infection and mortality is Staphylococcus lugdunensis (S. lugdunensis). It can cause harmless skin infections to life-threatening endocardial complications. We would like to report a rare presentation of S. lugdunensis bacteremia from a lymphocele that developed post surgery. An 80-year-old male presented to the emergency department with complaints of abdominal pain and fevers. Cultures of lymphocele fluid grew S. lugdunensis. A computed tomography of the abdomen and pelvis with contrast showed the presence of a large lymphocele. S. lugdunensis is a coagulase-negative staphylococci normally known to be a skin colonizer. Over the years, it has shown to cause a wide variety of infections especially involving prosthetic joints and heart valves. S. lugdunensis has been noted to be highly susceptible to penicillins, such as oxacillin, erythromycin, linezolid and a wide a variety of other antibiotics. S. lugdunensis produces a biofilm that makes treatment challenging even with susceptible antibiotics. However, the data on S. lugdunensis is growing as more case reports are being published in regards to source and susceptibilities.

Predicting survival in cancer patients with and without 30-day readmission of an unplanned hospitalization using a deficit accumulation approach.

BACKGROUND: For cancer patients with an unplanned hospitalization, estimating survival has been limited. We examined factors predicting survival and investigated the concept of using a deficit-accumulation survival index (DASI) in this population. METHODS: Data were abstracted from medical records of 145 patients who had an unplanned 30-day readmission between 01/01/16 and 09/30/16. Comparison data were obtained for patients who were admitted as close in time to the date of index admission of a study patient, but who did not experience a readmission within 30 days of their discharge date. Our survival analysis compared those readmitted within 30 days versus those who were not. Scores from 23 medical record elements used in our DASI system categorized patients into low-, moderate-, and high-score groups. RESULTS: Thirty-day readmission was strongly associated with the survival (adjusted hazard ratio [HR] 2.39; 95% confidence interval [CI], 1.46-3.92). Patients readmitted within 30 days of discharge from index admission had a median survival of 147 days (95% CI, 85-207) versus patients not readmitted who had not reached median survival by the end of the study (P < .0001). DASI was useful in predicting the survival; median survival time was 78 days (95% CI, 61-131) for the high score, 318 days (95% CI, 207-426) for the moderate score, and not reached as of 426 days (95% CI, 251 to undetermined) for the low-score DASI group (P < .0001). CONCLUSIONS: Patients readmitted within 30 days of an unplanned hospitalization are at higher risk of mortality than those not readmitted. A novel DASI developed from clinical documentation may help to predict survival in this population.

Genetic Investigation of Uterine Carcinosarcoma: Case Report and Cohort Analysis.

BACKGROUND: Uterine carcinosarcoma, a rare gynecological malignancy, often presents at the advanced stage with a poor prognosis because current therapies have not improved rates of survival. Genetic characterization of this tumor may lead to novel, specifically targeted drug targets to provide better treatment options for patients with this malignancy. METHODS: We present a case of a woman aged 61 years with uterine carcinosarcoma and retrospectively analyzed 100 study patients with uterine carcinosarcoma. From this group, 9 study patients underwent targeted sequencing of 1,321 genes. RESULTS: All 9 study patients had at least 1 mutation in JAK2, KRAS, PIK3CA, CTNNB1, PTEN, FBXW7, TP53, and ERBB2; of these, TP53 was the most frequently mutated gene (6/9). In addition, ARID1A and KMT2C, which have been described and identified as part of a set of chromatin-remodeling genes, were also found in our analyses. From our 100-person cohort clinical analyses, study patients with stage 1 cancer had a median survival rate of 33 months (95% confidence interval, 19-109) compared with a median survival rate of 6 months (95% confidence interval, 3-12) in those with stage 4 disease. CONCLUSIONS: Disease stage alone predicted the rate of clinical survival. Up to 50% in the study group were identified at having early stage disease (stage 1/2), indicating improved rates of overall detection compared with previously reported data. Our mutational analysis findings add to the number of tumors in which these mutations have been found and suggest that chromatin-remodeling dysregulation may play a role in the tumorigenesis of carcinosarcoma.