Unresolved Palliative Care Needs of Elderly Non-Cancer Patients at Home: A Multicenter Prospective Study.

INTRODUCTION/OBJECTIVES: There is growing consensus on the benefits of initiating palliative care early in the disease trajectory; however, palliative care needs for non-cancer patients remain to be elucidated. We investigated the trajectory of unresolved palliative care needs of non-cancer patients at home and explored associated factors. METHODS: We conducted a multicenter prospective cohort study of elderly non-cancer patients at home in Japan between Jan 2020 and Dec 2020. Physicians assessed their palliative care needs using the Integrated Palliative Care Outcome Scale (IPOS). Unresolved palliative care needs were defined as IPOS symptoms above 2 (moderate). RESULTS: In total, 785 patients were enrolled. The most frequent unresolved palliative care needs at enrollment were poor mobility (n = 438, 55.8%), followed by weakness/lack of energy (n = 181, 23.1%) and poor appetite (n = 160, 20.4%). Multivariate logistic regression analysis revealed that female and musculoskeletal disease were significantly positively associated with pain at starting home visits (OR = 1.89, P = .015; OR = 2.69, P = .005). In addition, neurological diseases were significantly positively associated with constipation and poor mobility 3 months after starting home visits (OR = 3.75, P = .047; OR = 3.04, P = .009). CONCLUSIONS: The order of the prevalence of unresolved palliative care needs may remain relatively stable over time, even for those receiving home-based palliative care services. We identified several specific diseases and conditions that were significantly associated with unresolved palliative care needs.

Transcatheter aortic valve replacement failure: a case report of the bicuspid aortic valve type 0 with a single coronary artery.

Transcatheter aortic valve replacement (TAVR) is the treatment of choice for aortic stenosis. However, its safety and efficacy in patients with the bicuspid aortic valve (BAV) remain controversial. Especially, whether the BAV phenotype affects outcomes following TAVR remains debated. Despite the higher ellipticity index and more calcifications of the aortic annulus in type 1 BAV, a high residual gradient was observed in type 0 anatomy. Moreover, severe calcification of the cusps rather than aortic annulus in type 0 is predisposed to asymmetrical under-expansion of the prosthesis at the edge of the native aortic cusp. We report the rare case of a patient with BAV stenosis type 0 and single coronary artery receiving TAVR, subsequently requiring surgical aortic valve replacement. The extensive non-coronary cusp calcification caused under-expansion of the prosthesis and was protruded into the left ventricular outflow tract, leading to an obstruction.

Trifecta versus Perimount Magna Ease aortic valves: Failure mechanisms.

BACKGROUND: There are increasing reports of early externally mounted pericardial Trifecta bioprosthesis failure. We compared the hemodynamic performance of Trifecta and Carpentier-Edwards Perimount Magna Ease valves to determine the failure mechanism. METHODS: We retrospectively included 270 consecutive patients (age: 73.4 ± 8.2 years; 57.5% male; mean follow-up: 48.0 ± 20.3 months) who underwent aortic valve replacement from 2014 to 2021 at a single center and compared the Trifecta (N = 137) and Carpentier-Edwards Perimount Magna Ease valve (N = 133) patients. RESULTS: The prosthetic valve major aortic regurgitation incidence was higher for the Trifecta than that for the Carpentier-Edwards Perimount Magna Ease valve (6.3% vs. 0%, P < 0.009). Among the Trifecta failures, 33% developed structural valve deterioration, but all requiring redo aortic valve replacement developed major prosthetic valve aortic regurgitation. Freedom at 5 years from redo aortic valve replacement due to structural valve deterioration was significantly lower for Trifecta (89.4% vs. 100%, P = 0.003). The reoperation hazards were determined for Trifecta (vs. Carpentier-Edwards Perimount Magna Ease): 11.6 (1.47-90.9; P = 0.02), prosthetic valve aortic regurgitation: 2.38 (1.70-3.32; P < 0.01), structural valve deterioration: 20.82 (4.08-106.2; P < 0.01), 5-year mean transprosthetic pressure gradient: 1.14 per 1-point increase (1.03-1.24; P = 0.007), and urgent surgery: 10.1 (2.59-39.0; P = 0.001). The Cox regression analysis identified that prosthetic valve aortic regurgitation solely contributed to redo aortic valve replacement (hazard ratio: 2.38; confidence intervals: 1.70-3.32). CONCLUSIONS: Significantly, more early failures occurred with the Trifecta valve than the Carpentier-Edwards Perimount Magna Ease valve but the Trifecta showed reasonable mean transprosthetic pressure gradient over time. Prosthetic valve aortic regurgitation and calcific structural valve deterioration synergistically contributed to Trifecta valve failure alternatively.

Activation and detection of HTLV-I Tax-specific CTLs by epitope expressing single-chain trimers of MHC class I in a rat model.

BACKGROUND: Human T cell leukemia virus type I (HTLV-I) causes adult T-cell leukemia (ATL) in infected individuals after a long incubation period. Immunological studies have suggested that insufficient host T cell response to HTLV-I is a potential risk factor for ATL. To understand the relationship between host T cell response and HTLV-I pathogenesis in a rat model system, we have developed an activation and detection system of HTLV-I Tax-specific cytotoxic T lymphocytes (CTLs) by Epitope expressing Single-Chain Trimers (SCTs) of MHC class I. RESULTS: We have established expression vectors which encode SCTs of rat MHC-I (RT1.Al) with Tax180-188 peptide. Human cell lines transfected with the established expression vectors were able to induce IFN-gamma and TNF-alpha production by a Tax180-188-specific CTL line, 4O1/C8. We have further fused the C-terminus of SCTs to EGFP and established cells expressing SCT-EGFP fusion protein on the surface. By co-cultivating the cells with 4O1/C8, we have confirmed that the epitope-specific CTLs acquired SCT-EGFP fusion proteins and that these EGFP-possessed CTLs were detectable by flow cytometric analysis. CONCLUSION: We have generated a SCT of rat MHC-I linked to Tax epitope peptide, which can be applicable for the induction of Tax-specific CTLs in rat model systems of HTLV-I infection. We have also established a detection system of Tax-specific CTLs by using cells expressing SCTs fused with EGFP. These systems will be useful tools in understanding the role of HTLV-I specific CTLs in HTLV-I pathogenesis.

Combining Scores Based on Compensatory and Noncompensatory Scoring Rules to Assess Resident Readiness for Unsupervised Practice: Implications From a National Primary Care Certification Examination in Japan.

PURPOSE: Competence decisions in health professions education require combining scores from multiple sources and identifying pass-fail decisions based on noncompensatory (required to pass all subcomponents) and compensatory scoring decisions. This study investigates consequences of combining scores, reliability, and implications for validity using a national examination with subcomponent assessments. METHOD: National data were used from three years (2015, 2016, and 2017) of the Japan Primary Care Association Board Certification Examination, with four subcomponent assessments: Clinical Skills Assessment-Integrated Clinical Encounter (CSA-ICE), CSA-Communication and Interpersonal Skills (CSA-CIS), Multiple-Choice Questions (MCQ), and Portfolio. Generalizability theory was used to estimate variance components and reliability. Kane's composite reliability and kappa decision consistency were used to examine the impact of using compensatory and noncompensatory scoring. RESULTS: Mean performance (n = 251) on the CSA-ICE, CSA-CIS, MCQ, and Portfolio subcomponent assessments were, respectively, 61% (SD = 11%), 67% (SD = 13%), 74% (SD = 8%), and 65% (SD = 9%); component-specific Φ-coefficient reliability ranged between, respectively, 0.57 and 0.67; 0.50 and 0.60; 0.65 and 0.76; and 0.87 and 0.89. Using a completely noncompensatory scoring approach on all four subcomponents, decision-consistency reliability was 0.33. Fully compensatory scoring yielded reliability of 0.86. CONCLUSIONS: Assessing a range of abilities in making entrustment decisions requires considering the balance of assessment tools measuring distinct but related competencies. These results indicate that noncompensatory pass-fail decision making, which seems more congruent with competency-based education, may lead to much lower reliability than compensatory decision making when several assessment subcomponents are used.

Functional analysis of Foxp3 and CTLA-4 expressing HTLV-1-infected cells in a rat model.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). Some ATL cells express Foxp3, which is known as regulatory T cell (Treg cell) specific transcription factor. It is suggested that Treg cell like suppressive activity of Foxp3 expressing ATL cells is associated to ATL development and related immunodeficiency. To develop an HTLV-1 model system that enables to investigate the association of Treg function in ATL progression, we examined the expression of Foxp3 and CTLA-4, Treg cell-associated factor, in established HTLV-1-infected rat cell lines and their regulatory function. We found the expression of Foxp3 in 10 of 22 and CTLA-4 in 10 of 19 HTLV-1-infected rat cell lines. Moreover, some of the Foxp3 and/or CTLA-4 expressing cell lines suppressed proliferation of naïve T cells that were stimulated with anti-CD3 antibody. Particularly all Foxp3(+) CTLA-4(+) cells showed the suppressive activity. Our data suggest the usefulness of our rat model systems for further analysis of the role of Treg cell-associated factors on the development of ATL and related immunodeficiency in vivo.

Enhanced replication of human T-cell leukemia virus type 1 in T cells from transgenic rats expressing human CRM1 that is regulated in a natural manner.

Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL). To develop a better animal model for the investigation of HTLV-1 infection, we established a transgenic (Tg) rat carrying the human CRM1 (hCRM1) gene, which encodes a viral RNA transporter that is a species-specific restriction factor. At first we found that CRM1 expression is elaborately regulated through a pathway involving protein kinase C during lymphocyte activation, initially by posttranscriptional and subsequently by transcriptional mechanisms. This fact led us to use an hCRM1-containing bacterial artificial chromosome clone, which would harbor the entire regulatory and coding regions of the CRM1 gene. The Tg rats expressed hCRM1 protein in a manner similar to expression of intrinsic rat CRM1 in various organs. HTLV-1-infected T-cell lines derived from these Tg rats produced 100- to 10,000-fold more HTLV-1 than did T cells from wild-type rats, and the absolute levels of HTLV-1 were similar to those produced by human T cells. We also observed enhancement of the dissemination of HTLV-1 to the thymus in the Tg rats after intraperitoneal inoculation, although the proviral loads were low in both wild-type and Tg rats. These results support the essential role of hCRM1 in proper HTLV-1 replication and suggest the importance of this Tg rat as an animal model for HTLV-1.