The impact of prolonged disorders of consciousness on family caregivers’ quality of life – a scoping review

Providing long-term care for a family member diagnosed with a Prolonged Disorder of Consciousness (PDoC) can have a significant impact on the lives of family caregivers. This scoping review aimed to explore the current literature investigating the impact of caring for a person in a PDoC on family caregivers’ Quality of Life (QOL), as categorized using the WHOQOL-BREF model. We observed that articles employing quantitative methodologies mostly reported QOL outcomes relating to negative feelings, thinking, learning, memory and concentration, and personal relationships. Articles employing qualitative methodologies mostly reported QOL outcomes relating to negative feelings, personal relationships, positive feelings, and health and social care accessibility and quality. A descriptive content analysis of the QOL outcomes highlighted the limitations of the current literature base in representing the complexities of the experiences of family members providing care for a person in a PDoC. To provide valuable and personalized support to caregivers, without pathologizing or medicalizing their distress, it is vital to characterize more accurately the contextual subtleties of each person’s situation

Family caregivers’ sense-making of the results of functional neurodiagnostics for patients with Prolonged Disorders of Consciousness

Functional neuroimaging and electrophysiological assessments can identify evidence of residual consciousness and cognition in patients with prolonged disorders of consciousness (PDOC) who are otherwise behaviourally unresponsive. These functional neurodiagnostics are increasingly available in clinical settings and are recommended by international clinical guidelines to reduce diagnostic and prognostic uncertainty, and thereby assist family caregivers in their best-interests decision-making. Nevertheless, little is known about how family caregivers make sense of the results of these state-of-the-art functional neurodiagnostics. By applying Interpretative Phenomenological Analysis (IPA) to interviews with family caregivers of patients with diagnoses of PDOC who had received a functional neurodiagnostic assessment, we identify three primary themes of sense-making: The special significance of “brain scans”; A dynamic sense-making process; Holding on to hope and holding on to the person. These themes highlight the challenges of helping family caregivers to balance the relative importance of functional neurodiagnostic results with other clinical assessments and identify an ability of family caregivers to hold a contradiction in which they hope for recovery but simultaneously express a rational understanding of evidence to the contrary. We offer several recommendations for the ways in which family caregivers can be better supported to make sense of the results of functional neurodiagnostics

The shaping of English literature and the readers' share in the development of its forms,

"... An attempt to tell the story of English readers from the days of the Saxons to the end of the eighteenth century."--p. 4.Printed in Great Britain.Mode of access: Internet

The shaping of English literature and the readers' share in the development of its forms,

"... An attempt to tell the story of English readers from the days of the Saxons to the end of the eighteenth century."--p. 4.Printed in Great Britain.Mode of access: Internet

Surgical Management of Melanoma-In-Situ Using a Staged Marginal and Central Excision Technique

Melanoma-in-situ (MIS) represents 45% of all melanomas. The margins of MIS are often poorly defined with extensive subclinical disease. Standard fusiform excision with 5-mm margins results in positive margins in up to a third of cases. To decrease the incidence of involved margins, we use a staged excision approach for MIS. First, patients undergo excision under local anesthesia of a 2- to 3-mm “contoured” rim of tissue optimally 5 mm beyond the visible extent of the lesion. Formalin-fixed paraffin-embedded en face sections from this excision are then evaluated, if necessary with the aid of immunohistochemical stains. Any positive margins are further excised. When all margins are negative, the central area is then excised and reconstructed. A total of 61 patients with MIS or lentigo maligna melanoma underwent staged contoured excisions from 2004 to 2007 at Moffitt Cancer Center. We analyzed data only from patients with MIS of the head and neck. Patients with known invasive melanoma or non–head and neck primary disease were excluded. Demographics, tumor characteristics, margin status, number of stages, and type of reconstruction and recurrences were evaluated. Forty-nine patients with MIS of the head and neck, 28 (57%) male and 21 (43%) female, 42 to 88-years-old (median 72; mean 70), underwent staged contoured margin excision before definitive central tumor excision and reconstruction. The final surgical defect size ranged from 2 to 130 cm2 (median 16 cm2). Twelve patients (24%) required reexcision of at least one margin; the median number of reexcisions was 1 (range 1–2). There seemed to be a positive association between lesion size and margin status (as well as number of excisions needed to clear the margin). Unsuspected invasive melanoma was found in the central specimen in six patients (12%). Even small tumors could have unsuspected invasive melanoma: invasive cancer was seen in 4 (21%) of 19 tumors ≤2 cm in greatest dimension and 2 (7%) of 30 > 2 cm, respectively. Surgical defects were reconstructed with flaps in 18 (37%), full-thickness grafts in 20 (41%), and split-thickness grafts in 10 patients (20%). Median time from first margin excision to completion/final reconstruction was 7 days (range 7–63 days). No local recurrences have been reported at a median follow-up of 14 months (range 1–36 months). This technique allows for careful margin analysis and subsequent central tumor excision with simultaneous reconstruction. This approach minimizes the need for a second major operation, which would have been necessary in 24% of our patients if treated by a one-stage excisional approach. It is noteworthy that 12% of MIS patients had invasive melanoma in the final excision specimen. This reinforces the importance of adequate full-thickness biopsies of suspicious pigmented lesions before any type of surgical management. With short follow-up, local control has been achieved by this technique in 100% of cases

Current surgical management of melanoma

The surgical management of melanoma has changed dramatically over the last few decades. Through the development and conduction of well-designed, prospective, randomized trials, we have been able to refine the way that we surgically manage patients with melanoma. Indeed, many important issues have been addressed through such trials: the proper surgical margins for the primary melanoma, utility of the elective lymph node dissection and the role for selective lymphadenectomy, to name a few. This review will also discuss what we have learned from past clinical trials and address several issues with regards to where we are going in the future

The transcriptional landscape of αβ T cell differentiation.

The differentiation of αβT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the known unknowns of thymocyte differentiation

The transcriptional landscape of αβ T cell differentiation.

The differentiation of αβT cells from thymic precursors is a complex process essential for adaptive immunity. Here we exploited the breadth of expression data sets from the Immunological Genome Project to analyze how the differentiation of thymic precursors gives rise to mature T cell transcriptomes. We found that early T cell commitment was driven by unexpectedly gradual changes. In contrast, transit through the CD4(+)CD8(+) stage involved a global shutdown of housekeeping genes that is rare among cells of the immune system and correlated tightly with expression of the transcription factor c-Myc. Selection driven by major histocompatibility complex (MHC) molecules promoted a large-scale transcriptional reactivation. We identified distinct signatures that marked cells destined for positive selection versus apoptotic deletion. Differences in the expression of unexpectedly few genes accompanied commitment to the CD4(+) or CD8(+) lineage, a similarity that carried through to peripheral T cells and their activation, demonstrated by mass cytometry phosphoproteomics. The transcripts newly identified as encoding candidate mediators of key transitions help define the 'known unknowns' of thymocyte differentiation