Palliative psychiatry for a patient with treatment-refractory schizophrenia and severe chronic malignant catatonia: case report.

BACKGROUND: Palliative psychiatry is an emerging field that suggests a role for palliative interventions in the management of severe and persistent mental illness (SPMI). Current literature describes using a palliative approach for patients with severe anorexia nervosa. To our knowledge, this is the first case report describing end-of-life care in a patient with treatment-refractory catatonic schizophrenia. CASE DESCRIPTION: We describe the case of a 49-year-old man with schizophrenia and severe chronic agitated/malignant catatonia who was hospitalized for ten months. Multiple treatment trials including medication such as neuroleptics and benzodiazepines, electroconvulsive therapy, and empiric interventions such as intravenous immunoglobulins were either not tolerated or did not result in clinically significant improvement. The patient continued to intermittently require intubation and sedation to control intractable behavioral and psychiatric disturbances. Ultimately, with collaboration of psychiatry, neurology, ethics, intensive care, and palliative care teams, the patient's parents decided to forgo further diagnostic testing and life-sustaining treatments. The patient died weeks later of aspiration pneumonia with good symptom control. CONCLUSIONS: This case permits discussion of palliative interventions in patients with SPMI such as treatment-refractory psychotic disorders who likely cannot achieve a quality of life that is acceptable to them. Here, it can be justified to prioritize relief of suffering and prevention of further burdensome interventions over treatment of the SPMI symptoms such as catatonia and even over keeping the patient alive.

Therapist self-disclosure: Let's tackle the elephant in the room.

Therapist Self-Disclosure (TSD), the revealing of a therapist's feelings, thoughts or personal information to a client, is an inevitable aspect of therapeutic relationships. However, despite its prevalence in clinical settings, we believe there is insufficient recognition and exploration of TSD in our work with children and adolescents. Because TSD is not often formally addressed during training, therapists across the spectrum of clinical child psychology and psychiatry are often left with the belief that disclosures are rare or inherently negative occurrences that should be avoided. As a byproduct, therapists often develop a blind spot to many disclosures that they make and are thus underprepared to navigate the complex decision-making process that surrounds TSD. In our article, we address the elephant in the room: that most therapists disclose in some form or other. In addressing this topic, we hope to encourage replacement of avoidance and silence with discourse and reflection around TSD occurrences. We explore developmental considerations pertinent to child and adolescent clients as well as suggest a framework for TSD decisions. We feel that improved supervision and clinical practice around TSD is a worthy and achievable aim that merits further recognition, consideration and educational focus.

First do no harm: Preventing harm and optimizing care in psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are challenging clinical occurrences consisting of any combination of altered movement, sensation, or awareness that resemble epileptic seizures (ES) but do not coincide with electrographic ictal discharges and are presumed to be neuropsychiatric-neurobehavioral in origin. Securing the PNES diagnosis is a crucial first step and is best confirmed by recording events on video-electroencephalogram (v-EEG) and finding an absence of ictal EEG changes and the presence of normal awake EEG rhythms before, during, and after the event. However, obstacles to timely diagnosis and referral to psychiatric treatment frequently occur, placing these patients at risk for harm from unnecessary medications and procedure as well as placing high burden on medical systems. Although providers across all disciplines share the responsibility by maintaining high suspicion of PNES in relevant clinical settings and engaging swiftly and empathically in securing and sharing the diagnosis with patients and families, psychiatric and neurologic providers are uniquely positioned to help lead patients towards safe and effective long-term care through a cohesive approach that is rooted in therapeutic alliance, interdisciplinary collaboration, and realistic treatment goals.

Recombinant vaccinia virus GLV-1h68 is a promising oncolytic vector in the treatment of cholangiocarcinoma.

Although early stage cholangiocarcinoma (CC) can be cured by surgical extirpation, the options for treatment of advanced stage CC are very few and suboptimal. Oncolytic virotherapy using replication-competent vaccinia virus (VACV) is a promising new strategy to treat human cancers. The ability of oncolytic VACV GLV-1h68 to infect, replicate in, and lyse three human CC cell lines was assayed in vitro and in subcutaneous flank xenografts in athymic nude mice. In this study, we have demonstrated that GLV-1h68 effectively infects and lyses three CC cell lines (KMC-1, KMBC, and KMCH-1) in vitro. Expression of the viral marker gene ruc-gfp facilitated real-time monitoring of infection and replication. Furthermore in athymic nude mice, a single dose of GLV-1h68 significantly suppressed tumor growth. The treatment was well tolerated in all animals. Recombinant VACV GLV-1h68 has significant oncolytic ability against CC both in vitro and in vivo. GLV-1h68 has the potential to be used clinically as a therapeutic agent against CC.

Oncolytic gene therapy with recombinant vaccinia strain GLV-2b372 efficiently kills hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) commonly presents at a late stage when surgery is no longer a curative option. As such, novel therapies for advanced HCC are needed. Oncolytic viruses are a viable option for cancer therapy owing to their ability to specifically infect, replicate within, and kill cancer cells. In this study, we have investigated the ability of GLV-2b372, a novel light-emitting recombinant vaccinia virus derived from a wild-type Lister strain, to kill HCC. METHODS: Four human HCC cell lines were assayed in vitro for infectivity and cytotoxicity. Viral replication was quantified via standard viral plaque assays. Flank HCC xenografts generated in athymic nude mice were treated with intratumoral GLV-2b372 to assess for tumor growth inhibition and viral biodistribution. RESULTS: Infectivity occurred in a time- and concentration-dependent manner with 70% cell death in all cell lines by day 5. All cell lines supported efficient viral replication. At 25 days after infection, flank tumor volumes decreased by 50% whereas controls increased by 400%. Tumor tissue demonstrated substantial GLV-2b372 infection at 24 hours, 48 hours, and 2 weeks. CONCLUSION: We demonstrate that GLV-2b372 efficiently kills human HCC in vitro and in vivo and is a viable treatment option for patients with HCC.

Gene therapy using therapeutic and diagnostic recombinant oncolytic vaccinia virus GLV-1h153 for management of colorectal peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis (PC) is a terminal progression of colorectal cancer (CRC). Poor response to cytoreductive operation and chemotherapy coupled with the inability to reliably track disease progression by the use of established diagnostic methods, make this a deadly disease. We examined the effectiveness of the oncolytic vaccinia virus GLV-1h153 as a therapeutic and diagnostic vehicle. We believe that viral expression of the human sodium iodide transporter (hNIS) provides both real-time monitoring of viral therapy and effective treatment of colorectal peritoneal carcinomatosis (CRPC). METHODS: Infectivity and cytotoxic effect of GLV-1h153 on CRC cell lines was assayed in vitro. Viral replication was examined by standard viral plaque assays. Orthotopic CRPC xenografts were generated in athymic nude mice and subsequently administered GLV-1h153 intraperitoneally. A decrease in tumor burden was assessed by mass. Orthotopic tumors were visualized by single-photon emission computed tomography/computed tomography after Iodine ((131)I) administration and by fluorescence optical imaging. RESULTS: GLV-1h153 infected and killed CRC cells in a time- and concentration-dependent manner. Viral replication demonstrated greater than a 2.35 log increase in titer over 4 days. Intraperitoneal treatment of orthotopic CRPC xenografts resulted in a substantial decrease in tumor burden. Infection of orthotopic xenografts was therapeutic and facilitated monitoring by (131)I-single-photon emission computed tomography/computed tomography via expression of hNIS in infected tissue. CONCLUSION: GLV-1h153 kills CRC in vitro effectively and decreases tumor burden in vivo. We demonstrate that GLV-1h153 can be used as an agent to provide accurate delineation of tumor burden in vivo. These findings indicate that GLV-1h153 has potential for use as a therapeutic and diagnostic agent in the treatment of CRPC.

Oncolytic immunotherapy using recombinant vaccinia virus GLV-1h68 kills sorafenib-resistant hepatocellular carcinoma efficiently.

BACKGROUND: Sorafenib is the standard systemic therapy for unresectable or recurrent hepatocellular carcinoma (HCC) but adds minimal increase in survival. Therefore, there is a great need to develop novel therapies for advanced or recurrent HCC. One emerging field of cancer treatment involves oncolytic viruses that specifically infect, replicate within, and kill cancer cells. In this study, we examined the ability of GLV-1h68, a recombinant vaccinia virus derived from the vaccine strain that was used to eradicate smallpox, to kill sorafenib-resistant (SR) HCC cell lines. METHODS: Four SR HCC cell lines were generated by repeated passage in the presence of sorafenib. Median inhibitory concentration was determined for all cell lines. The infectivity, viral replication, and cytotoxicity of GLV-1h68 were assayed for both parental and SR HCC cells. RESULTS: Infectivity increased in a time and concentration-dependent manner in all cell lines. All cell lines supported efficient replication of virus. No difference between the rates of cell death between the parental and SR cell lines was observed. CONCLUSION: Our results demonstrate that the oncolytic vaccinia virus GLV-1h68 kills both parental and SR HCC cell lines efficiently. This study indicates that patients who have failed treatment with sorafenib remain viable candidates for oncolytic therapy.