Experiences, challenges and perspectives for ensuring end-of-life patient care: A national online survey with general practitioners in Germany.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic is posing major challenges for health care systems. In Germany, one such challenge has been that adequate palliative care for the severely ill and dying (with and without COVID-19), as well as their loved ones, has not been available at all times and in all settings., the pandemic has underlined the significance of the contribution of general practitioners (GPs) to the care of severely ill and dying patients. OBJECTIVES: To describe GPs' experiences, challenges and perspectives with respect to end-of-life care during the first peak of the pandemic (spring 2020) in Germany. MATERIALS AND METHODS: In November and December 2020, a link to an Unipark online survey was sent to GPs registered on nationwide distribution lists. RESULTS: In total, 410 GPs responded; 61.5% indicated that the quality of their patients' end-of-life care was maintained throughout the pandemic, 36.8% reported a decrease in quality compared to pre-pandemic times. Of the GPs who made home visits to severely ill and dying patients, 61.4% reported a stable number of visits, 28.5% reported fewer visits. 62.7% of the GPs reported increased telephone contact and reduced personal contact with patients; 36.1% offered video consultations in lieu of face-to-face contact. The GPs reported that relatives were restricted (48.5%) or prohibited from visiting (33.4%) patients in nursing homes. They observed a fear of loneliness among patients in nursing homes (91.9%), private homes (87.3%) and hospitals (86.1%). CONCLUSIONS: The present work provides insights into the pandemic management of GPs and supports the development of a national strategy for palliative care during a pandemic. To effectively address end-of-life care, GPs and palliative care specialists should be involved in COVID-19 task forces on micro, meso and macro levels of health care.

[Outpatient care of oncological patients in palliative treatment situations and their relatives during the COVID-19 pandemic]. / Ambulante Betreuung onkologischer Patienten in palliativer Behandlungssituation und ihrer Angehörigen in der COVID-19-Pandemie: Erfahrungen, Herausforderungen und Lösungsansätze niedergelassener Onkologen.

BACKGROUND: During the current pandemic situation, the public health care system must ensure the ongoing provision of regular medical care as well as the treatment of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infected patients. Resident oncologists and their practices are equally affected. OBJECTIVES: The study examines resident oncologists' challenges, experiences and approaches in the delivery of care for oncological patients receiving palliative treatment and their relatives during the pandemic. Findings will support future pandemic preparedness for cancer treatment in outpatients. MATERIALS AND METHODS: Content analyses of 13 guideline-based telephone interviews with resident oncologists. RESULTS: Solid local networks, staff and structural rearrangements and infection control within offices helped oncologists maintaining quality of care. Required treatments have been continued. The interrupted information flow towards patients' relatives and catching up on previously postponed primary, control or follow-up consultations have been reported as a challenge. Other issues have been linked to suspected SARS-CoV­2 infection in patients and staff. The lack of information, temporal inaccessibility of health care authorities and physicians' associations, and additional costs for infection control material caused further problems. CONCLUSIONS: Due to the firmly implemented infection control and the re-organisation of facilities and staff, oncologists have been able to maintain treatment and care for cancer patients and their relatives. Hygiene procedures proved to work well and might be re-activated. An increased use of digital applications for treatment monitoring might be considered. Furthermore, solutions to meet additional financial and personnel demands caused by infection control must be identified. The design of suitable concepts for the prevention of health-related hazards due to visiting bans for relatives and therapeutic staff such as physio- and occupational therapists is inevitable.

ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2.

The co-stimulators ICOS (inducible T cell co-stimulator) and CD28 are both important for T follicular helper (TFH) cells, yet their individual contributions are unclear. Here, we show that each molecule plays an exclusive role at different stages of TFH cell development. While CD28 regulated early expression of the master transcription factor Bcl-6, ICOS co-stimulation was essential to maintain the phenotype by regulating the novel TFH transcription factor Klf2 via Foxo1. Klf2 directly binds to Cxcr5, Ccr7, Psgl-1, and S1pr1, and low levels of Klf2 were essential to maintain this typical TFH homing receptor pattern. Blocking ICOS resulted in relocation of fully developed TFH cells back to the T cell zone and reversion of their phenotype to non-TFH effector cells, which ultimately resulted in breakdown of the germinal center response. Our study describes for the first time the exclusive role of ICOS and its downstream signaling in the maintenance of TFH cells by controlling their anatomical localization in the B cell follicle.

T-follicular helper cells survive as long-term memory cells.

T-follicular helper (TFH) cells represent the subpopulation of CD4(+) T cells that provides help for antigen-specific B cells in the GC response. They are generated from naïve T cells during an immune response and are imprinted by their master transcription factor Bcl-6. It has been a long-standing question if TFH cells contribute to the CD4(+) memory pool after the GC response has been terminated. To answer this question, we sorted antigen-specific TFH and non-TFH effector cells from an ongoing GC response and transferred them into naïve mice. Without further signals via the TCR, transferred cells rapidly contracted with a small population of both TFH and non-TFH cells surviving as memory cells in peripheral lymphoid organs for at least 4 weeks in the absence of antigen. TFH cells strongly downregulated their signature genes Bcl-6, CXCR5, and PD-1 in the memory phase. Upon rechallenge with antigen they rapidly upregulated these markers again. An enhanced potential to produce IL-21, paired with higher expression of CXCR5 and lower expression of CCR7, should enable TFH memory cells to provide more efficient help for antigen-specific B cells than their non-TFH counterparts.

Reduced Treg frequency in LFA-1-deficient mice allows enhanced T effector differentiation and pathology in EAE.

The αLß2-integrin LFA-1 (CD11a/CD18) is known as an important molecule for leukocyte migration. However, the precise role of LFA-1 in the pathogenesis of EAE has so far remained unclear. We describe here the disease development in LFA-1(-/-) mice compared with WT controls. Ablation of LFA-1 resulted in more severe EAE with increased demyelination and increased numbers of myelin oligodendrocyte glycoprotein-reactive CD4(+) T cells in the CNS. However, the production of the pro-inflammatory cytokines IL-17 and IFN-γ was unchanged on the level of antigen-specific T cells. Interestingly, LFA-1-deficient mice showed a clearly reduced frequency of Treg in the inflamed CNS. Moreover, Treg counts in spleens and thymi of unimmunized LFA-1(-/-) mice were lower in comparison to the WT controls, indicating an impairment of Treg generation. In combination, these results suggest a substantial role of LFA-1 in Treg generation and subsequent expansion of effector T cells and highlight the importance of Treg in limiting EAE.

Synthesis of citrate-ciprofloxacin conjugates.

Two regioisomeric citrate-functionalized ciprofloxacin conjugates have been synthesized and their antimicrobial activities against a panel of clinically-relevant bacteria have been determined. Cellular uptake mechanisms were investigated using wild-type and ompF deletion strains of Escherichia coli K-12.