Catatonia After Liver Transplantation.

BACKGROUND Central nervous system complications after transplantation occur in up to 40% of recipients and these complications are associated with increased length of hospital stay and mortality. Catatonia is a neuropsychiatric clinical syndrome which has been described in case reports and in a small case series as occurring in the immediate post-solid organ transplantation (SOT) period, and it has been attributed to calcineurin inhibitor neurotoxicity, psychological vulnerability, and depression. Among transplant recipients, the incidence of catatonia is unknown; it may be under diagnosed in part due to a broad differential diagnosis in the post-transplantation setting, which includes hypoactive delirium, non-convulsive status epilepticus, drug toxicity, conversion disorder, and volitional uncooperativeness. CASE REPORT We present 2 cases of catatonia diagnosed in liver allograft recipients. We also reviewed current literature for cases of catatonia among SOT recipients. We provide provisional evaluation and management strategies of recipients with clinical concern for catatonia. Catatonia generally occurs within the few first days after liver transplantation, and presents with staring, immobility, or mutism, but is also associated with other neurological and psychiatric symptoms. Catatonia can be successfully treated with intravenous lorazepam, and thus, modifying immunosuppressive regimens may be avoidable. Medications to treat catatonia are generally tapered over weeks to months, and psychiatric follow-up is indicated. The early post-liver transplantation period may be a state of relative deficiency in GABA (gamma-aminobutyric acid) signaling, predisposing liver transplant recipients in particular to post-transplantation catatonia. CONCLUSIONS Despite difficulties in establishing the diagnosis, catatonia after liver transplantation was rapidly responsive to intravenous lorazepam, indicating that changing immunosuppressants may be avoidable.

Clinical Characteristics and Outcomes Associated With High-Dose Intravenous Thiamine Administration in Patients With Encephalopathy.

BACKGROUND: Wernicke encephalopathy is a common neuropsychiatric syndrome due to thiamine deficiency. There is no consensus regarding thiamine dosing when Wernicke encephalopathy is suspected. A longstanding dosing strategy for Wernicke encephalopathy is 100mg daily, yet updated clinical guidelines suggest using high-dose intravenous (HDIV) thiamine. OBJECTIVE: To describe thiamine prescribing practices at a large, public academic hospital and investigate clinical characteristics and outcomes associated with HDIV thiamine in patients with encephalopathy who received IV thiamine. METHODS: Electronic medical records of hospitalized patients who received thiamine between 4/4/2014 and 11/1/2015 were reviewed. Chi-square tests, Wilcoxon Rank Sum tests, and logistic regression were used to compare clinical variables in patients with encephalopathy who received HDIV thiamine (≥ 200mg twice daily) vs lower doses of IV thiamine. RESULTS: Among the total of 5236 thiamine orders, 29% (n = 1531) were IV; 10% (n = 150) of IV orders met HDIV criteria. In patients with encephalopathy who received IV thiamine (n = 432), HDIV thiamine was administered to 20% (n = 86) and only 2.1% (n = 9) received dosing consistent with Royal College of Physicians guidelines. In bivariable analyses, HDIV thiamine was associated with surgical services (p = 0.001), psychiatric consultation (p < 0.001), and decreased mortality (p = 0.004). In multivariable models, the association between HDIV thiamine and decreased in-hospital mortality did not meet statistical significance (p = 0.061). CONCLUSIONS: In a large, public academic hospital, guideline-concordant thiamine supplementation is rare and HDIV thiamine is infrequently prescribed to patients with encephalopathy. Further studies are needed to confirm the possible benefits of HDIV thiamine for patients with suspected thiamine-deficient encephalopathy.

Cardiometabolic Assessment, Diagnosis, and Treatment of Chronic Medical Illnesses During an Inpatient Psychiatric Hospitalization: Colocated Medical Care Versus Treatment as Usual.

BACKGROUND: Reverse colocation care models reduce lifestyle risk factors, emergency department visits, and readmissions. Persons with serious mental illness have higher than average rates of cardiovascular disease-related morbidity and mortality, with second-generation antipsychotics (SGAs) conferring added related risks. Little is written about reverse colocated medical care (RCL) in inpatient psychiatric settings. The objective of this study was to identify associations between screening, diagnosis, and treatment of chronic medical comorbidities and mode of medical care for patients discharged from 2 inpatient psychiatric units on SGAs. METHODS: This was a cross-sectional retrospective study of medical comorbidities identified and treated for adults consecutively admitted from January 1, 2015, to October 31, 2015, to 2 inpatient psychiatry units of an academic center and discharged on SGAs. One unit has a primary care team consisting of a physician assistant backed up by a medical doctor who provide medical care (RCL). The other unit has medical care provided by psychiatrists with hospitalists as needed (treatment as usual, TAU). We conducted a chart review of demographics, vital signs, laboratory values, diagnoses, and medications with comparative analysis of the evaluation, diagnosis, and treatment for hypertension, diabetes mellitus, hyperlipidemia, obesity, and tobacco use disorder. RESULTS: In total, 232 patients were discharged from the TAU group and 220 from the RCL group. Significantly more screening laboratory values (glucose, hemoglobin A1c, lipids) were obtained in the TAU group, while documented responses to abnormal tests were higher in the RCL group. Patients were more likely in the RCL group to be diagnosed with obesity, tobacco use disorder, and hyperlipidemia and to be treated for hypertension and hyperlipidemia. CONCLUSIONS: Reverse colocated medical care is effective in improving screening, diagnosis, and treatment of chronic medical diseases among psychiatric inpatients.​.

Anatomical considerations for endoscopic endonasal skull base surgery in pediatric patients.

OBJECTIVES/HYPOTHESIS: Pediatric skull base surgery is limited by several boney sinonasal landmarks that must be overcome prior to tumor dissection. When approaching a sellar or parasellar tumor, the piriform aperture, sphenoid sinus pneumatization, and intercarotid distances are areas of potential limitation. Quantitative pediatric anatomical measurements relevant to skull base approaches are lacking. Our goal was to use radio-anatomic analysis of computed tomography scans to determine anatomical limitations for trans-sphenoidal approaches in pediatric skull base surgery. STUDY DESIGN: A radio-anatomic cross-sectional survey. METHODS: Measurements included the diameter of the piriform aperture, posterior extent of sphenoid sinus pneumatization, and intercarotid distances on fine-cut, age-stratified maxillofacial scans. Fifty pediatric (<18 years of age) and 10 adult patients were equally subdivided into seven age groups and compared to determine age-related differences in sphenoid sinus pneumatization, skull base thicknesses, and intercarotid distances. RESULTS: Piriform aperture width was significantly greater in adults than in patients under age 7 years (P

In vitro modeling of nonhypoxic cold ischemia-reperfusion simulating lung transplantation.

OBJECTIVE: Although anoxia/reoxygenation of cultured cells has been used to model lung ischemia-reperfusion injury, this does not accurately mimic events experienced by lung cells while a lung is retrieved from a donor, stored, and transplanted. We developed an in vitro model of nonhypoxic ischemia-reperfusion injury to simulate these events. METHODS: Human umbilical vein endothelial cells underwent simulated cold ischemia by replacing 37 degrees C culture media with 4 degrees C Perfadex (Vitrolife, Kungsbacka, Sweden) solution for 5 hours in 100% O(2). Culture dishes were allowed to warm to room temperature for 1 hour (implantation), and then Perfadex solution was replaced with 37 degrees C culture media (reperfusion). RESULTS: During cold ischemia, the human umbilical vein endothelial cell filamentous actin cytoskeleton quickly became rearranged, and gaps developed in the previously confluent monolayer occupying 20% of the surface area. Simulated reperfusion resulted in reorganization to a confluent monolayer. Development of gaps was not due to enhanced necrosis based on lactate dehydrogenase retention assay. Endothelial cytoskeletal rearrangement could account for early edema caused by ischemia-reperfusion injury with reperfusion. Mitogen-activated protein kinase and nuclear factor kappaB activation occurred with simulated reperfusion despite normoxia. Levels of the proinflammatory cytokines interleukin 6 and interleukin 8 were significantly increased in media at the end of reperfusion. CONCLUSIONS: Exposing human umbilical vein endothelial cells to simulated cold ischemia without hypoxia causes reversible cytoskeletal alterations, activation of inflammatory pathways, and elaboration of cytokines. Because this model accurately depicts events occurring during lung transplantation, it will be useful to explore mechanisms regulating lung cell response to this unique form of ischemia-reperfusion injury.

Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edema.

Toll-like receptors (TLRs) of the innate immune system contribute to noninfectious inflammatory processes. We employed a murine model of hilar clamping (1 h) with reperfusion times between 15 min and 3 h in TLR4-sufficient (C3H/OuJ) and TLR4-deficient (C3H/HeJ) anesthetized mice with additional studies in chimeric and myeloid differentiation factor 88 (MyD88)- and TLR4-deficient mice to determine the role of TLR4 in lung ischemia-reperfusion injury. Human pulmonary microvascular endothelial monolayers were subjected to simulated warm ischemia and reperfusion with and without CRX-526, a competitive TLR4 inhibitor. Functional TLR4 solely on pulmonary parenchymal cells, not bone marrow-derived cells, mediates early lung edema following ischemia-reperfusion independent of MyD88. Activation of MAPKs and NF-kappaB was significantly blunted and/or delayed in lungs of TLR4-deficient mice as a consequence of ischemia-reperfusion injury, but edema development appeared to be independent of activation of these signaling pathways. Pretreatment with a competitive TLR4 inhibitor prevented edema in vivo and reduced actin cytoskeletal rearrangement and gap formation in pulmonary microvascular endothelial monolayers subjected to simulated warm ischemia and reperfusion. In addition to its well-accepted role to alter gene transcription, functioning TLR4 on pulmonary parenchymal cells plays a key role in very early and profound pulmonary edema in murine lung ischemia-reperfusion injury. This may be due to a novel mechanism: regulation of endothelial cell cytoskeleton affecting microvascular endothelial cell permeability.

Bcl-2 suppresses sarcoplasmic/endoplasmic reticulum Ca2+-ATPase expression in cystic fibrosis airways: role in oxidant-mediated cell death.

RATIONALE: Modulation of the activity of sarcoendoplasmic reticulum calcium ATPase (SERCA) can profoundly affect Ca(2+) homeostasis. Although altered calcium homeostasis is a characteristic of cystic fibrosis (CF), the role of SERCA is unknown. OBJECTIVES: This study provides a comprehensive investigation of expression and activity of SERCA in CF airway epithelium. A detailed study of the mechanisms underlying SERCA changes and its consequences was also undertaken. METHODS: Lung tissue samples (bronchus and bronchiole) from subjects with and without CF were evaluated by immunohistochemistry. Protein and mRNA expression in primary non-CF and CF cells was determined by Western and Northern blots. MEASUREMENTS AND MAIN RESULTS: SERCA2 expression was decreased in bronchial and bronchiolar epithelia of subjects with CF. SERCA2 expression in lysates of polarized tracheobronchial epithelial cells from subjects with CF was decreased by 67% as compared with those from subjects without CF. Several non-CF and CF airway epithelial cell lines were also probed. SERCA2 expression and activity were consistently decreased in CF cell lines. Adenoviral expression of mutant F508 cystic fibrosis transmembrane regulator gene (CFTR), inhibition of CFTR function pharmacologically (CFTR(inh)172), or stable expression of antisense oligonucleotides to inhibit CFTR expression caused decreased SERCA2 expression. In CF cells, SERCA2 interacted with Bcl-2, leading to its displacement from caveolae-related domains of endoplasmic reticulum membranes, as demonstrated in sucrose density gradient centrifugation and immunoprecipitation studies. Knockdown of SERCA2 using siRNA enhanced epithelial cell death due to ozone, hydrogen peroxide, and TNF-alpha. CONCLUSIONS: Reduced SERCA2 expression may alter calcium signaling and apoptosis in CF. These findings decrease the likelihood of therapeutic benefit of SERCA inhibition in CF.