Regorafenib for patients with progression of advanced hepatocellular carcinoma after treatment with atezolizumab plus bevacizumab: a case series.

Background: Immunotherapy has reshaped the systemic treatment of hepatocellular carcinoma (HCC), with atezolizumab plus bevacizumab (TA) regimen and regorafenib being the first-line and second-line treatment options for advanced HCC, respectively. However, the efficacy of using the second-line therapeutic agent regorafenib in patients with HCC that has progressed after TA regimen treatment is unknown, and there is a lack of supporting clinical data. The purpose of this case series was to evaluate the clinical efficacy of the second-line therapeutic agent regorafenib in patients with advanced HCC who progressed after treatment with a first-line TA regimen. Case Description: This case series included five patients with intermediate to advanced HCC treated with regorafenib after progression on a TA regimen. We retrospectively report the clinical data, clinical outcomes, and adverse events of these five patients. According to modified Response Evaluation Criteria in Solid Tumors (mRECIST), one patient achieved partial response (PR), three patients achieved stable disease (SD), and one patient experienced progressive disease (PD); the disease control rate (DCR) reached 80%, and the objective response rate (ORR) reached 20%. Conclusions: In patients with intermediate to advanced HCC who experience disease progression after TA therapy, second-line treatment with regorafenib may be effective in delaying progression and may be associated with better disease control. However, these findings need to be further confirmed in prospective studies with larger cohorts.

Using Interdisciplinary Teams to Mitigate the Effects of Drug Shortages in Palliative Care: The Case of Lorazepam Injection.

Given the rising frequency of drug shortages in hospitals, interdisciplinary collaboration is necessary to manage medications, modify electronic medical records, and evaluate safety outcomes. One such shortage impacted lorazepam injection, a medication commonly used in palliative care to treat anxiety, agitation, and seizures. In anticipation of the lorazepam shortage in the summer of 2022, pharmacy staff collaborated with palliative care physicians to identify alternative treatment recommendations when providers were prohibited from ordering lorazepam injection. Before the shortage, lorazepam was used an average of 95 times per month on the palliative care unit. The overall use of benzodiazepines decreased substantially following the recommendation for the therapeutic alternative, midazolam, during the shortage. Once the shortage ended, use roughly returned to pre-shortage baselines. During this time, there were no patient safety events documented on the palliative care unit. Moreover, no changes to the care experience were reported by patients, family/caregivers, providers, or staff. The collaborative effort between pharmacy and palliative care specialists resulted in alternative treatments for palliative care patients during the drug shortage. This preserved the hospital's supply of lorazepam injection for a patient population with no suitable alternatives while still allowing for management of palliative patients.

A narrative review of supportive and end of life care considerations in advanced hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths, and case numbers continue to rise in the United States. HCC carries a poor prognosis, and management requires a multidisciplinary approach. This narrative review aims to identify opportunities for further integration of palliative care (PC) in HCC care. Given the high symptom burden faced by patients with HCC, early PC consultation can be beneficial for patients. METHODS: A search of PubMed was conducted from inception of the database to March 1, 2023. The search was composed of keywords and controlled vocabulary terms for concepts related to palliative medicine and symptom management in the setting of HCC. KEY CONTENT AND FINDINGS: This narrative review finds that although PC has been integrated into HCC guidelines, partnerships between PC and hepatology are still nascent in clinical practice. Treatment-related barriers pose a challenge to timely integration of PC in the care of HCC patients; evaluation or listing for transplantation can be perceived as a barrier to PC consultation, and unpredictable clinical courses make prognostication challenging. Providers may hesitate to pursue PC referral due to a lack of consensus around the role of PC, and for those that are referred, timing of consultation remains an issue, especially for those who are potential liver transplant candidates. There are few studies of PC in HCC, limiting evidence-based recommendations that can be made regarding PC involvement in this patient population. CONCLUSIONS: While PC is not routinely integrated into HCC care, recent guideline recommendations and a growing number of studies may change this over time. Although further evidence is needed, PC and hepatology teams partnering together can explore ways to improve the care of this patient population. PC consultation early in HCC care could assist in management of symptom relief, psychosocial and spiritual support, and caregiver support. Effective communication will be required to set parameters for referral and clarify potential outcomes of consultation. Teams should be prepared for the challenges involved in a culture change and paradigm shift in clinical practice.

Implementing Palliative Care Interdisciplinary Teams: Consultative Versus Integrative Models.

Interdisciplinary teams are at the core of intensive care unit palliative care consultation. They allow health professionals of different disciplines to collaborate in a synergistic fashion to achieve the goals of patients and their families. Interdisciplinary teams can have a variety of members depending on available resources and the goals for its function. There are multiple benefits to highly functioning teams, as well as challenges that may be faced when trying to provide patient care in a team-based setting. Interdisciplinary teams of different structures may provide the ideal support for complex cases in critical care settings.

Discontinuance of life sustaining treatment utilizing ketamine for symptom management.

We present the case of an otherwise healthy 21-year-old female who developed severe respiratory failure following a minor procedure requiring ECMO and bi-level ventilation. During her protracted ICU course, she had significant difficulties with agitation and was titrated to the following regimen: hydromorphone 30 mg/hour, fentanyl 200 mcg/hour, dexmedetomidine 1.5 mcg/kg/hour, propofol at 70 mcg/kg/min, and midazolam at 20 mg/hour. We were consulted to assist in withdrawal of life prolonging measures at the family's request and given high doses of commonly used opioid and sedative medications successfully utilized methadone and ketamine for symptom control. This case study would indicate that in selected patients on high dose opioid and sedative medications prior to withdrawal of life prolonging measures ketamine may be considered for symptom management.

Management of refractory status epilepticus in an actively dying patient.

No consensus guidelines exist for the treatment of refractory myoclonic status epilepticus or refractory myoclonus in the palliative care setting. Evidence-based guidelines for the general medical population are often neither practical nor applicable at the end of life. Many challenges, including medication availability, route of administration, monitoring, and work-up are all unique to the palliative care setting. Two patients with refractory myoclonus versus refractory myoclonic status epilepticus are described here, illustrating the challenges involved in treatment as well the need for further research for therapy in the palliative care setting.

Oral ketamine for sickle cell crisis pain refractory to opioids.

There is literature demonstrating that the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has analgesic properties that can be used as an adjuvant to opiates for pain relief in multiple various conditions and pain states. However, there is a lack of published information on ketamine used in persons with sickle cell disease in acute pain crises. The Virginia Commonwealth University Palliative Care team was consulted on a 38-year-old African American female with sickle cell thalassemia in severe acute pain crisis overlying chronic pain related to her disease. Pain control was unable to be achieved with escalating doses of opiates and other adjuvant medications. The patient responded well to an intravenous test dose of ketamine and was subsequently placed on an oral regimen of ketamine in addition to opiates. In the 24-hour period following ketamine initiation, the patient's pain was able to be controlled on decreased amounts of opiates. She was eventually transitioned to an oral opiate and ketamine regimen, which allowed her to be discharged home with pain levels close to her baseline and the ability to function and perform all activities of daily living.