Clinical Impasse Research Articles

Conquering dual challenges: A sialic acid-modified liposome for targeting activated neutrophils to tackle comorbid lung inflammation and cancer metastasis

In clinical settings, cancer frequently coexists with multi-system diseases. Owing to compromised immune systems, patients with cancer exhibit an increased susceptibility to infections and inflammation. Notably, lung inflammation occurs with high incidence among these patients. Furthermore, the inflammatory milieu within the lungs often accelerates the metastasis of cancer, thereby enhancing mortality rates and posing substantial challenges for clinical management. To date, effective strategies addressing both lung inflammation and cancer concurrently are lacking. In this context, we introduce a novel therapeutic approach involving a sialic acid-lipid derivative (SA-PG10-C18) modified doxorubicin-curcumin co-loaded liposome (DOX/CUR-SAL). This formulation effectively targeted activated neutrophils, which are abundantly present in inflammatory and metastatic lung tissues. DOX/CUR-SAL notably inhibited neutrophil-mediated pro-inflammatory and pro-metastatic processes. Utilizing a newly established mouse model of acute lung injury (ALI) and metastasis comorbidity, DOX/CUR-SAL modulated the lung immune microenvironment and arrested the progression of both inflammation and metastasis, without inducing side effects. The treated animals demonstrated favorable survival conditions, persisting beyond 45 days. This innovative therapeutic strategy offers a novel concept and reference for treating comorbid conditions of tumors and inflammation, thus breaking the clinical impasse where lung inflammation and cancer metastasis have been treated separately.

The enchanted unconscious, impasses, negotiation and surrender: Jeremy Safran in dialogue with the Rebbes of Ishbitz/Radzin.

Dr. Jeremy Safran had a unique talent to seamlessly weave together clinical work with his broad knowledge of philosophy, history, and theology. Alongside his commitment to researching the minutest clinical interactions, he was conscious of the broad values of the nature of the good life that underpinned his analytic approach. This paper will explore the concepts of the enchanted unconscious, clinical impasses, negotiation, and surrender, suggesting that these concepts together provide insight into Safran's larger philosophy of life. It will then provide the approach to these concepts of the Rebbes of Ishbitz/Radzin, a school of Polish Hasidic thought. It will conclude with an exploration of how both Safran's psychoanalytic approach and the Ishbitz/Radzin Rebbes' Hasidic approach to the Torah provide distinct insights and applications of these concepts, which can be mutually enriching for both disciplines.

Reflective group supervision: psychotherapists and child health centre nurses in collaboration

ABSTRACT Postpartum depression affects every sixth mother, and emotional distress in infants is also common. The need for parent-infant consultations and psychotherapies probably greatly exceeds the number of families who in fact receive qualified help. Nurses at child health centres are the first professionals to meet distressed families. Their readiness to help them is clouded by conflicting professional attitudes, patients’ expectations, and uncertainties of how to handle patient-nurse interactions. Nurses may experience clinical impasses that need attention. Reflective group supervision can be a valuable remedy, and a method for educating nurses in daily practice. The method is illustrated by a vignette, and a review of the nursing and psychoanalytic literature. Nurses often address problems with anger, guilt, and anxiety of uncertainty, which may block their understanding of the families’ emotional entanglements. Supervision combines the supervisor’s psychodynamic competence and the nurses’ experiences, to inspire self-reflection on difficult cases. It should be provided regularly with management support, and the supervisor should preferably be a psychotherapist experienced in child and adult work. The therapist can work simultaneously as a consultant clinician at the centre, thus increasing the opportunities for families to receive adequate help.

Drawing a Blank: Bion Speaking on Chinese Writing

Wilfred Bion briefly discussed Chinese writing some dozen times, attributing to it various counter-intuitive features. A review of these passages suggests they were part of Bion's larger effort to evoke the challenges of bridging communication gaps with patients, where Bion held that the very means of communication itself was at issue. Chinese also helped evoke a sense of mystery in listeners who, like Bion, knew no Chinese. The main source of Bion's Sinology, an influential 1908 essay by Ernest Fenollosa, was broadly discredited by the 1950's, yet Bion propounded it in five countries through the 1970's. Psychoanalysis, not linguistics, was his subject as he used a mystifying intellectual fantasy (of a Chinese cognitive Other) to discuss incomprehension—a state of unknowing common to clinical impasse and to a philosophical mindset. That Bion induced (deliberately or not) a receptively confused mental state in listeners as he discussed written Chinese, is consistent with discerning observations of Bion's presentations by Leo Rangel and Donald Meltzer. Bion's claims about Chinese are largely false; more interestingly, they are largely incoherent, yet he used them again and again. That they have evaded critical scrutiny these fifty years may be due to the same effects they produced in performance.

The Romani Woman and the (non)Wandering Jew: Immigration, Dissociation, and The Search for Belonging

The author writes about growing up with her complex and enigmatic immigrant father, who lived many years as a stigmatized other, a Russian Jew in northern China. She focuses on the impact this personal family history has on her treatment with a female Romani patient from Eastern Europe, a more recent immigrant, who also lived many years as a stigmatized other. The author differentiates between the experience of one-time immigrants and migrants, the latter being haunted by generations of dislocation, which causes them to question their fundamental sense of safety and belonging. The author discusses the ways the personal and professional threads become interwoven in the work, impacting the bi-directional conscious and unconscious flow of the treatment. Together patient and analyst build toward a mutually transformative moment, following a clinical impasse.

Direct Oral Anticoagulants in Patients on Chronic Dialysis and Concomitant Atrial Fibrillation: A Common Clinical Impasse.

The most frequent arrhythmia treated is atrial fibrillation (AF), which necessitates the use of oral anticoagulants (OACs) to reduce the risk of thromboembolism and stroke. Patients with chronic kidney disease are more likely to develop AF, with a 10% frequency among those on chronic dialysis. Warfarin is the most widely prescribed OAC for individuals with end-stage kidney disease (ESKD). On the other hand, direct OACs (DOACs) are generally safer than warfarin, with fewer fatal bleeding events and a fixed dose that does not require close international normalized ratio (INR) monitoring. For those patients, warfarin and apixaban appear to be FDA-approved, whereas dabigatran, rivaroxaban, and edoxaban are not recommended yet. Due to a lack of large randomized studies, data from major trials cannot be extended to dialysis patients. In this review, we summarize the available data and literature referring to patients on chronic hemodialysis with concomitant AF. Due to the scarcity of data, we try to assist clinicians in selecting the appropriate therapy according to the specific characteristics of each patient. Finally, future directions are provided in two key areas of focus: left atrial appendage closure therapies and genetic research.

Osteosarcoma and Metastasis.

Osteosarcoma is the most common primary bone malignancy in adolescents. Its high propensity to metastasize is the leading cause for treatment failure and poor prognosis. Although the research of osteosarcoma has greatly expanded in the past decades, the knowledge and new therapy strategies targeting metastatic progression remain sparse. The prognosis of patients with metastasis is still unsatisfactory. There is resonating urgency for a thorough and deeper understanding of molecular mechanisms underlying osteosarcoma to develop innovative therapies targeting metastasis. Toward the goal of elaborating the characteristics and biological behavior of metastatic osteosarcoma, it is essential to combine the diverse investigations that are performed at molecular, cellular, and animal levels from basic research to clinical translation spanning chemical, physical sciences, and biology. This review focuses on the metastatic process, regulatory networks involving key molecules and signaling pathways, the role of microenvironment, osteoclast, angiogenesis, metabolism, immunity, and noncoding RNAs in osteosarcoma metastasis. The aim of this review is to provide an overview of current research advances, with the hope to discovery druggable targets and promising therapy strategies for osteosarcoma metastasis and thus to overcome this clinical impasse.

Holding Multiple Perspectives in Mind: The Dialectics of Contemporary Clinical Practice

In this paper, we explore the dialectical nature of psychoanalytic social work practice and the benefits - theoretical and clinical - of doing so. We posit being mindful of the dialectic 1) aides us in our effort to identify and speak to differing themes, each of which is understood to be a piece of glass in the mosaic that is the totality of the client’s experience as a human being, 2) enhances our awareness of what might be going on in the clinical moment, particularly the shared ­experience between client and clinician, and 3) facilitates holding multiple perspectives in mind. On the other hand, non-­acknowledgement of the dialectical nature of our theories and interventions seems linked with moments of clinical impasse and fuels the false dichotomies that often confront psychoanalytic social workers, individually and collectively. Appreciation of the dialectic can help us overcome these challenges and enables us to conceptualize our work as a process of becoming, which we see as highly relevant to clinical work with pressing contemporary issues such as trauma, diversity, and the theme of access. We demonstrate these claims through two vignettes, one explicitly clinical and the other an example of contextual factors affecting practice, to show how dialectical thinking allows for a deepening of things both inside and outside the consulting room.

The Ethics of Feeding the Aspirating Child in an Age of Increasing Patient Complexity.

The Ethics of Feeding the Aspirating Child in an Age of Increasing Patient Complexity.

Using action methods in clinical supervision: a journey from talk to action

ABSTRACT Clinical supervision is a critical tool in the professional development of psychotherapists of all types including social workers, counselors and marriage and family therapists. “Clinical training” or “clinical consultation” are also terms that describe the process of a clinician seeking the advice or perspective of a more experienced clinician or expert. Most clinical supervisors use talk to help their supervisees gain skills in assessment and intervention, develop confidence, overcome obstacles coming from biases and blind spots, and feel support. Action methods are usually overlooked as a way to help supervisees develop and to overcome clinical impasse with their clients. In this paper I will share my journey from “talk supervisor” to “action supervisor.” This paper will demonstrate the power of action methods, developed by Jacob Moreno, to help supervisors and the therapists they work with to gain clarity, deepen understanding, view cases with a fresh eye, work through difficult emotional experiences, and explore unconscious assumptions, beliefs, and values that can interfere with treatment. Case examples are included.

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression.

Osteosarcoma is a malignant primary tumor of bone, arising from transformed progenitor cells with osteoblastic differentiation and osteoid production. While categorized as a rare tumor, most patients diagnosed with osteosarcoma are adolescents in their second decade of life and underscores the potential for life changing consequences in this vulnerable population. In the setting of localized disease, conventional treatment for osteosarcoma affords a cure rate approaching 70%; however, survival for patients suffering from metastatic disease remain disappointing with only 20% of individuals being alive past 5 years post-diagnosis. In patients with incurable disease, pulmonary metastases remain the leading cause for osteosarcoma-associated mortality; yet identifying new strategies for combating metastatic progression remains at a scientific and clinical impasse, with no significant advancements for the past four decades. While there is resonating clinical urgency for newer and more effective treatment options for managing osteosarcoma metastases, the discovery of druggable targets and development of innovative therapies for inhibiting metastatic progression will require a deeper and more detailed understanding of osteosarcoma metastasis biology. Toward the goal of illuminating the processes involved in cancer metastasis, a convergent science approach inclusive of diverse disciplines spanning the biology and physical science domains can offer novel and synergistic perspectives, inventive, and sophisticated model systems, and disruptive experimental approaches that can accelerate the discovery and characterization of key processes operative during metastatic progression. Through the lens of trans-disciplinary research, the field of comparative oncology is uniquely positioned to advance new discoveries in metastasis biology toward impactful clinical translation through the inclusion of pet dogs diagnosed with metastatic osteosarcoma. Given the spontaneous course of osteosarcoma development in the context of real-time tumor microenvironmental cues and immune mechanisms, pet dogs are distinctively valuable in translational modeling given their faithful recapitulation of metastatic disease progression as occurs in humans. Pet dogs can be leveraged for the exploration of novel therapies that exploit tumor cell vulnerabilities, perturb local microenvironmental cues, and amplify immunologic recognition. In this capacity, pet dogs can serve as valuable corroborative models for realizing the science and best clinical practices necessary for understanding and combating osteosarcoma metastases.

Clínica da psicose em um hospital de custódia e tratamento psiquiátrico

Após contextualizar o projeto conjunto entre o Fórum do Campo Lacaniano/São Paulo e um hospital de custódia, apresentamos um caso clínico a respeito de um sujeito de estrutura psicótica. O objetivo dessa transmissão é apontar certos impasses e possibilidades importantes com relação à clínica com a psicose. A forma com que se transmitem esses aspectos é por considerações sobre a transferência e os registros simbólico, imaginário e real, a partir dos quais elaboramos algumas questões. Tratamos da presença do analista como aspecto imaginário da transferência, da inversão da transferência específica aos casos de psicose, da possibilidade da autoria de músicas como um trabalho com o registro real e do trabalho com o delírio como um aspecto simbólico na transferência.

Impasses e alcances da psicanálise: o empreendedorismo do analista contemporâneo

O artigo apresenta uma pesquisa de cunho qualitativo realizada com psicanalistas, com significativa experiencia clinica e producao escrita sobre Psicanalise. Por meio de entrevistas semidirigidas, buscou-se explorar os efeitos das demandas clinicas contemporâneas na forma dos participantes exercerem a clinica e, tambem, suas concepcoes a respeito da atual situacao da Psicanalise. Os dados obtidos foram trabalhados com o metodo de Analise de Conteudo e resultaram na estruturacao de quatro Categorias Finais: Incompletude e abertura da Psicanalise: o valor do legado de Freud; A clinica psicanalitica atual: exigencia de trabalho ao psicanalista; O ouro da Psicanalise; e, por ultimo, O enfrentamento do mal-estar proprio da Psicanalise: riscos e potenciais. Os achados deste estudo permitiram definir como empreendedorismo o trabalho criativo do psicanalista diante de impasses clinicos e nomear como analista contemporâneo o profissional que, compromissado com a essencia do legado freudiano, inquieta-se e cria frente aos interrogantes clinicos, produzindo, assim, conhecimento em Psicanalise.Palavras-chave: clinica psicanalitica, analista contemporâneo; Psicanalise, empreendedorismo.

Ultrasound Imaging of Mouse Fetal Intracranial Hemorrhage Due to Ischemia/Reperfusion.

Despite vast improvement in perinatal care during the 30 years, the incidence rate of neonatal encephalopathy remains unchanged without any further Progress towards preventive strategies for the clinical impasse. Antenatal brain injury including fetal intracranial hemorrhage caused by ischemia/reperfusion is known as one of the primary triggers of neonatal injury. However, the mechanisms of antenatal brain injury are poorly understood unless better predictive models of the disease are developed. Here we show a mouse model for fetal intracranial hemorrhage in vivo developed to investigate the actual timing of hypoxia-ischemic events and their related mechanisms of injury. Intrauterine growth restriction mouse fetuses were exposed to ischemia/reperfusion cycles by occluding and opening the uterine and ovarian arteries in the mother. The presence and timing of fetal intracranial hemorrhage caused by the ischemia/reperfusion were measured with histological observation and ultrasound imaging. Protein-restricted diet increased the risk of fetal intracranial hemorrhage. The monitoring of fetal brains by ultrasound B-mode imaging clarified that cerebral hemorrhage in the fetal brain occurred after the second ischemic period. Three-dimensional ultrasound power Doppler imaging visualized the disappearance of main blood flows in the fetal brain. These indicate a breakdown of cerebrovascular autoregulation which causes the fetal intracranial hemorrhage. This study supports the fact that the ischemia/reperfusion triggers cerebral hemorrhage in the fetal brain. The present method enables us to noninvasively create the cerebral hemorrhage in a fetus without directly touching the body but with repeated occlusion and opening of the uterine and ovarian arteries in the mother.

Clinicians’ Reverie as Private Enactments

This paper introduces a concept the authors refer to as private enactments. While the majority of the relational literature has focused on the more dramatic enactments in treatment, private enactments emerge as the therapist becomes aware through reveries and personal associations that she is facing a parallel struggle with the patient, one shaped by the unfolding relational unconscious cocreated in treatment. These moments are private in the sense that the therapist experiences them internally after a period of sustained, often confusing private reflection during moments of clinical impasse. The authors elucidate this process with two cases with traumatized patients that highlight how the eventual resolution of private enactments offered new perspective on the clinical stalemate, novel understanding that evolved into constructive interventions after both authors became aware of shared, dissociated conflicts involving threads of trauma and loss, leading further to mutual reparation. Far from being dramatic moments acted out between therapist and patient, or far from simply involving unresolved emotional conflicts in the therapist, the cases of help illustrate how these subtle, often unnoticed musings operating sub rosa can highlight a shared, cocreated struggle that if identified can provide new insight and relief from impasse, so that we change as our patients change by metabolizing our private associations.

Swimming Lessons: Aging, Dissociation, and Embodied Resonance

How do bodies communicate in the analytic relationship? What is the therapeutic action of embodied communication? In this paper, I examine the effects of a form of embodied communication that I refer to as “embodied resonance.” Using a model of mind that is comprised of multiple self states that become dissociated in response to trauma and that are carried, unsymbolized, in body and mind, I suggest that “embodied resonance” enables patient and analyst to make initial contact with dissociated self-states. Consequently, the analyst helps her patient understand, verbalize, and incorporate a greater and truer sense of himself into his life story. I present a detailed clinical example of my work with Jon, an elderly patient suffering from Alzheimer’s disease, to illustrate how understanding the impact of a patient’s traumatic past can be a freeing experience that allows him to come to terms with his particularly traumatic aging experience. Changes in self understanding were reflected in changes in my patient’s body and changes in his experience of himself as an aging person. I also suggest that whether implicitly known or explicitly verbalized, embodied resonance can offer enriching, mutative attachment experiences. Finally, the analyst’s somatic attunement to her own traumatic memories and dissociated self states is discussed as a way to inform clinical impasses in the analytic treatment.

The Transference is Indeed a Cross: Commentary on Paper by Sue Grand

Sue Grand presents a case of “a near-death clinical impasse,” conjuring “God at an impasse.” She questions the philosophical premises and culture biases that inform the foundations of psychoanalytic theory. She asks how we rewrite “the psychoanalytic subject.” This commentary explores the themes of clinical impasse, psychoanalysis and religion, martyrdom and self-sacrifice, the negative Oedipus or “Jacob complex,” multiplicity of selves, and psychoanalytic witnessing. Most important, it challenges the tendency to polarize the Jewish and Christian narratives such that Judaism is depicted as “this worldly” in contrast to Christianity, which is seen as celebrating martyrdom in identification with Christ. It argues for psychoanalysis to recognize the spiritual value of submission and surrender without splitting them into polar oppositions.

God at an Impasse: Devotion, Social Justice, and the Psychoanalytic Subject

In this paper, a clinical impasse is used to study the philosophical premises and culture biases that inform the foundations of psychoanalytic theory. In his childhood, the patient was a migrant laborer, in a large Christian fundamentalist family. He survived through forming bonds with other children, in shared conditions of abjection. In adulthood, he has fulfilled the American Dream. And yet he suffers. He feels like anyone and no one, and is without individual subjectivity. Through his illness narrative, his devotional practices, and a near-death clinical impasse, he confronts the analyst with questions. What is missing from our psychoanalytic vision of the “family”? Can we recognize this patient in our current models of attachment? If psychoanalysis extrudes politics and culture and spirit and ethics, can we “mentalize” this patient? What happens when a patient has a collectivized self, and no individual psychology? What happens when a patient's Christian worldview is radically disjunctive with the Jewish ethos of psychoanalysis? Who is the psychoanalytic subject? Ultimately, the treatment argues for this: that we need to rewrite our understanding of the psychoanalytic subject.

Chemistry and Containing: the Analyst’s Use of Unavoidable Failures

Certain patients overwhelm the analyst’s capacity to contain both the patient and the analyst’s own unbearable feelings. Though some such failures of containing may lead fairly quickly to self-correction and others to clinical impasse, our focus is on an in-between state in which the analyst’s ability to tolerate his inevitable failures and gradually to (re)establish his containing capacities through difficult self-analytic work can lead to significant change that might not otherwise be possible. The authors argue that this internal psychological work on the analyst’s part, which may require considerable time, effort, and suffering, is an important aspect of “good enough” containing. The unique chemistry generated between patient and analyst plays an important role in both establishing and maintaining this kind of productive analytic process.

Contribuições de Sándor Ferenczi para a compreensão dos efeitos psíquicos da violência sexual

O presente trabalho consiste em um estudo teorico que apresenta os efeitos da violencia sexual na infância sob a otica de Sandor Ferenczi (1873-1933), psicanalista da primeira geracao dos discipulos de Freud o qual conferiu grande importância ao trauma sexual e ao papel do adulto na constituicao do psiquismo infantil. Serao analisadas suas contribuicoes - originadas da clinica com pacientes adultos que haviam sofrido abuso sexual na infância - privilegiando o artigo ferencziano, publicado em 1933, Confusao de lingua entre os adultos e a crianca. A fim de compreender determinados movimentos psiquicos marcados pela acao da clivagem psiquica, pretendemos examinar a descricao de dois arranjos psiquicos: a identificacao com o agressor e a progressao traumatica ou prematuracao, aportes teoricos ferenczianos que serao utilizados para uma reflexao clinica.