Essential PcsB putative peptidoglycan hydrolase interacts with the essential FtsXSpn cell division protein in Streptococcus pneumoniae D39.

The connection between peptidoglycan remodeling and cell division is poorly understood in ellipsoid-shaped ovococcus bacteria, such as the human respiratory pathogen Streptococcus pneumoniae. In S. pneumoniae, peptidoglycan homeostasis and stress are regulated by the WalRK (VicRK) two-component regulatory system, which positively regulates expression of the essential PcsB cysteine- and histidine-dependent aminohydrolases/peptidases (CHAP)-domain protein. CHAP-domain proteins usually act as peptidoglycan hydrolases, but purified PcsB lacks detectable enzymatic activity. To explore the functions of PcsB, its subcellular localization was determined. Fractionation experiments showed that cell-bound PcsB was located through hydrophobic interactions on the external membrane surface of pneumococcal cells. Immunofluorescent microscopy localized PcsB mainly to the septa and equators of dividing cells. Chemical cross-linking combined with immunoprecipitation showed that PcsB interacts with the cell division complex formed by membrane-bound FtsX(Spn) and cytoplasmic FtsE(Spn) ATPase, which structurally resemble an ABC transporter. Far Western blotting showed that this interaction was likely through the large extracellular loop of FtsX(Spn) and the amino terminal coiled-coil domain of PcsB. Unlike in Bacillus subtilis and Escherichia coli, we show that FtsX(Spn) and FtsE(Spn) are essential in S. pneumoniae. Consistent with an interaction between PcsB and FtsX(Spn), cells depleted of PcsB or FtsX(Spn) had strikingly similar defects in cell division, and depletion of FtsX(Spn) caused mislocalization of PcsB but not the FtsZ(Spn) early-division protein. A model is presented in which the interaction of the FtsEX(Spn) complex with PcsB activates its peptidoglycan hydrolysis activity and couples peptidoglycan remodeling to pneumococcal cell division.

Nomenclature in Palliative Surgery.

Surgical palliative care, palliative care interventions, and palliative surgery all reference a blend of these 2 sub-specialty fields. Despite prior published definitions, use of these phrases both clinically and in the literature is varied and can lead to confusion and misunderstanding. Herein, we proposed the adoption of standardized nomenclature to guide the consistent use of these phrases.

Palliative care interventions for surgical patients: a narrative review.

BACKGROUND AND OBJECTIVE: Palliative interventions have known benefits in the care of surgical patients with advanced illness. However, the literature supporting the routine use and implementation of palliative care in the context of surgery is limited. The primary aim of this review was to explore the literature that has been published in the field of surgical palliative care since 2016. The secondary aim of this analysis was to categorize updates in literature in three foundational domains (I) measuring outcomes that matter to patients; (II) communication and decision making; and (III) delivery of palliative care to surgical patients. METHODS: This analysis included citations from PubMed, EMBASE, PsychINFO, and CINAHL, circulated between 01/01/2016 and 22/02/2022 that studied palliative care interventions for surgical patients. Additional articles were included following a manual review of citations and publications from the Annals of Palliative Medicine. KEY CONTENT AND FINDINGS: A total of 3,258 unique articles were identified through the database search, and eight additional studies were identified from manual review. Twenty-two articles were included in the final narrative review: seven addressed the first foundational domain, three explored the second, and twelve summarized developments in the third. CONCLUSIONS: With advances in clinical opportunities to support seriously ill patients, the adoption of palliative care frameworks in surgical settings is essential to achieving value-concordant care. Though the literature studying the delivery of palliative care for surgical patients is slowly expanding, additional work is needed to optimize pre and post-operative patient engagement in complex decision making, align surgical treatments with patient-oriented outcomes, and integrate palliative care principles into routine surgical practice.

Discovery of asymptomatic moyamoya arteriopathy in pediatric syndromic populations: radiographic and clinical progression.

OBJECT: Limited data exist to guide management of incidentally discovered pediatric moyamoya. Best exemplified in the setting of unilateral moyamoya, in which the unaffected side is monitored, this phenomenon also occurs in populations undergoing routine surveillance of the cerebral vasculature for other conditions, such as sickle cell disease (SCD) or neurofibromatosis Type 1 (NF1). The authors present their experience with specific syndromic moyamoya populations to better characterize the natural history of radiographic and clinical progression in patients with asymptomatic moyamoya. METHODS: The authors performed a retrospective review of the clinical database of the neurosurgery department at Children's Hospital Boston, including both nonoperative referrals and a consecutive series of 418 patients who underwent surgical revascularization for moyamoya disease between 1988 and 2010. RESULTS: Within the period of time studied, 83 patients were asymptomatic at the time of radiographic diagnosis of moyamoya, while also having either unilateral moyamoya or moyamoya in association with either SCD or NF1. The mean age at presentation was 9.1 years (range 1-21 years), and there were 49 female (59%) and 34 male (41%) patients. The mean follow-up duration was 5.4 ± 3.8 years (mean ± SD), with 45 patients (54%) demonstrating radiographic progression and 37 (45%) becoming symptomatic within this period. Patients with SCD had the highest incidence of both radiographic (15 patients [75%]) and clinical (13 patients [65%]) progression, followed by NF1 (20 patients [59%] with radiographic progression and 15 patients [44%] with clinical progression) and patients with unilateral moyamoya (10 patients [35%] with radiographic progression and 9 patients [31%] with clinical progression). CONCLUSIONS: Radiographic progression occurred in the majority of asymptomatic patients and generally heralded subsequent clinical symptoms. These data demonstrate that moyamoya is a progressive disorder, even in asymptomatic populations, and support the rationale of early surgical intervention to minimize morbidity from stroke.

The Empathy Project: A Skills-Development Game: Innovations in Empathy Development.

CONTEXT: Empathy is increasingly described as a learnable skill and is included in professionalism requirements for health care providers, yet there are few effective tools for developing and practicing empathy skills. INNOVATION: An educational innovation intended to isolate and develop skills to respond to patients' emotions. The game-based tool was developed on the job during the authors' Hospice and Palliative Medicine fellowship year and was played with learners in various disciplines. OUTCOMES: Feedback from learners was overwhelmingly positive, although a key factor in optimization of learning was the presence of a communication expert as facilitator. Learner responses were measured using a novel assessment tool, and findings suggest statistically significant expansion of language and intent to express empathy. Learners demonstrated immediate growth in naming emotions, reflecting understanding and respect of emotional expression, and supporting and exploring emotional content. COMMENT: This innovative game-based learning tool is of low cost and feasible to deploy. It could be easily incorporated into medical education curricula aimed at developing communication skills, especially the skill of responding to emotion with empathy. Future research is needed to assess the effects the innovation has on behavior as well as its impact on patient-centered outcomes.

Discussing Prognosis and Shared Decision-Making.

When making high-stakes decisions with their patients, surgeons may have only one opportunity to get a life-changing conversation right. These loaded conversations cover immense ground. Bad news, emotion, prognosis, treatment choices, and patient goals all play a part in coming up with the right plan for each individual patient. Surgeons and patients may overlook important factors when the language and process of informed consent is substituted for decision-making. "Best Case/Worst Case" is a communication tool based in scenario planning that promotes shared decision-making in high-stakes surgical conversations and is discussed at length in this review.

Surgery Hurts: Characterizing the Experience of Pain in Surgical Patients as Witnessed by Medical Students.

BACKGROUND: The patient experience around surgical care is poorly characterized. Medical students have a unique position on the surgical team, which allows them to observe patient experiences that may otherwise be overlooked. The objective of this study was to characterize surgical patients' experience with pain as witnessed by medical students. STUDY DESIGN: At the end of an 8-week surgical clerkship, we asked all third-year medical students to write a reflective essay describing one surgical patient in pain. We collected 341 essays over a 4-year period and used qualitative content analysis to explore the students' reports of pain experienced by surgical patients. RESULTS: When asked to tell a story about a surgical patient in pain, medical students report vivid descriptions of physical agony, emotional distress, and patient regret. For example, "Throughout the procedure our patient cried out and writhed in agony from the searing pain in his chest," and "The patient was practically shedding tears, complaining of pain, as [we] changed her dressing." The students' accounts reveal wide-ranging physical and emotional suffering among surgical patients, including alterations in self-image and feelings of vulnerability. Pain and suffering were intensified when patients felt they had lost control, in settings of uncertain prognosis and with unexpected outcomes. CONCLUSIONS: Students' descriptions of the surgical patient's experience are disturbingly graphic. They expose suffering ranging from generalized discomfort to anguish and excruciating pain. These data suggest that surgical patients have substantial unmet needs with respect to symptom management and emotional support that, if better addressed, could improve the patient experience.

Third-Year Medical Students' Reactions to Surgical Patients in Pain: Doubt, Distress, and Depersonalization.

CONTEXT: Medical students have limited instruction about how to manage the interpersonal relationships required to care for patients in pain. OBJECTIVES: The objective of this study was to characterize the experiences of medical students as they encounter pain, suffering, and the emotional experiences of doctoring. METHODS: We used qualitative analysis to explore the content of 341 essays written by third-year medical students who described their experiences with surgical patients in pain. We used an inductive process to develop a coding taxonomy and then characterized the content of these essays related to empathy, patient-clinician interaction, and descriptions of clinical norms. RESULTS: Students found it difficult to reconcile patient suffering with the therapeutic objective of treatment. They feared an empathic response to pain might compromise the fortitude and efficiency required to be a doctor and they pursued strategies to distance themselves from these feelings. Students described tension around prescription of pain medications and worried about the side effects of medications used to treat pain. Students felt disillusioned when operations caused suffering without therapeutic benefit or were associated with unexpected complications. Although patients had expressed a desire for intervention, students worried that the burdens of treatment and long-term consequences were beyond patient imagination. CONCLUSION: These observations about patient-doctor relationships suggest that there is a larger problem among clinicians relating to patient distress and personal processing of the emotional nature of patient care. Efforts to address this problem will require explicit instruction in skills to develop a personal strategy for managing the emotionally challenging aspects of clinical work.

Molecular definition of a metastatic lung cancer state reveals a targetable CD109-Janus kinase-Stat axis.

Lung cancer is the leading cause of cancer deaths worldwide, with the majority of mortality resulting from metastatic spread. However, the molecular mechanism by which cancer cells acquire the ability to disseminate from primary tumors, seed distant organs, and grow into tissue-destructive metastases remains incompletely understood. We combined tumor barcoding in a mouse model of human lung adenocarcinoma with unbiased genomic approaches to identify a transcriptional program that confers metastatic ability and predicts patient survival. Small-scale in vivo screening identified several genes, including Cd109, that encode novel pro-metastatic factors. We uncovered signaling mediated by Janus kinases (Jaks) and the transcription factor Stat3 as a critical, pharmacologically targetable effector of CD109-driven lung cancer metastasis. In summary, by coupling the systematic genomic analysis of purified cancer cells in distinct malignant states from mouse models with extensive human validation, we uncovered several key regulators of metastatic ability, including an actionable pro-metastatic CD109-Jak-Stat3 axis.

Supporting Medical Students' Pursuit of Longitudinal Patient Experiences: Piloting an Innovative Visit Notification Tool at the Massachusetts General Hospital.

PROBLEM: Both medical educators and students have an increasing interest in longitudinal patient experiences (LPE) that allow students to work with patients at multiple points in time, often across multiple clinical settings. Despite this interest in LPE, following patients over time and across health systems remains a challenge. APPROACH: In August 2012-May 2013, with faculty support, two third-year medical students implemented a pilot program at the Massachusetts General Hospital (MGH) in the third-year block clerkship curriculum. One of the authors modified an existing novel, electronic visit notification tool (VNT) that integrates with the electronic medical record (EMR) to help students follow patients longitudinally. Students added patients to their cohort after obtaining the patient's verbal consent. Each week, the VNT sent students e-mails notifying them of all scheduled appointments for their cohort patients at all Partners HealthCare-affiliated sites. OUTCOMES: Each pilot student added approximately 20 patients to her cohort and followed 3-5 patients consistently. The pilot students felt the VNT made it significantly easier to follow patients over time, their appreciation of chronic illness care developed, and they gained a greater understanding of the integrated nature of patient care. NEXT STEPS: On the basis of student interest, the tool was made available to all MGH third-year students in March-May 2013 and offered to all MGH third-year students at the beginning of the next clinical year. Notification tools such as the VNT may enhance a hospital's existing EMR and facilitate longitudinal educational goals across all clinical clerkship models.

Neuroendocrine tumors of the pancreas: Degree of cystic component predicts prognosis.

BACKGROUND: Although most pancreatic neuroendocrine tumors are solid, approximately 10% are cystic. Some studies have suggested that cystic pancreatic neuroendocrine tumors are associated with a more favorable prognosis. METHODS: A retrospective review of all patients with pancreatic neuroendocrine tumors who underwent operative resection between 1999 and 2014 at a single academic medical center was performed. Based on cross-sectional imaging performed before operation, pancreatic neuroendocrine tumors were classified according to the size of the cystic component relative to the total tumor size: purely cystic (100%), mostly cystic (≥50%), mostly solid (<50%), and purely solid (0%). Clinicopathologic characteristics and recurrence-free survival were assessed between groups. RESULTS: In the study, 214 patients met inclusion criteria: 8 with purely cystic tumors, 7 with mostly cystic tumors, 15 with mostly solid tumors, and 184 with purely solid tumors. The groups differed in terms of tumor size (1.5 ± 0.5, 3.0 ± 1.7, 3.7 ± 2.6, and 4.0 ± 3.5 cm), lymph node positivity (0%, 0%, 26.7%, and 34.2%), intermediate or high grade (0%, 16.7%, 20.0%, and 31.0%), synchronous liver metastases (0%, 14.3%, 20.0%, and 26.6%) and need for pancreaticoduodenectomy (0%, 0%, 6.7%, and 25.0%), respectively. No cases of purely cystic pancreatic neuroendocrine tumors were associated with synchronous liver or lymph node metastasis, intermediate/high grade, recurrence, or death due to disease. Among patients presenting without metastatic disease, 10-year recurrence-free survival was 100% in patients with purely and mostly cystic tumors versus 53.0% in patients with purely and mostly solid tumors; however, this difference did not reach statistical significance. CONCLUSION: Pancreatic neuroendocrine tumors demonstrate a spectrum of biologic behavior with an increasing cystic component being associated with more favorable clinicopathologic features and prognosis. Purely cystic pancreatic neuroendocrine tumors may represent 1 subset that can be safely observed without immediate resection.