The Needs, Use and Expectations of People Bereaved by Suicide Regarding Online Resources: An Online Survey.

BACKGROUND: Online resources constitute a new and effective way to obtain support or information during bereavement processes. However, little is known about the needs, use and expectations of people bereaved by suicide regarding online resources. METHOD: The objective of our national cross-sectional online survey was to collect the use, needs and expectations of people bereaved by suicide regarding online resources. The data were collected from July to October 2021 through a 26-item online questionnaire hosted on the website LimeSurvey. RESULTS: A total of 401 respondents fully completed the questionnaire. Their mean age was 45.7. The majority of participants were women bereaved by the suicide of their child or partner. Half of the participants were bereaved for less than 3 years and benefited from counselling during their bereavement process. Three-quarters of the participants used the Internet for their bereavement process, mainly to obtain information on suicide bereavement and suicide prevention and to access testimonies of other people bereaved by suicide. Three-quarters of the participants found that available online resources for people bereaved by suicide are insufficient and expected a dedicated web platform to be developed. Finding information on suicide bereavement and on suicide prevention, discussing with a mental health professional and accessing testimonies of other people bereaved by suicide were expected by a majority of the participants regarding the future platform. Receiving counselling and being bereaved by the death of a child were the most important factors in explaining patterns of use and expectations regarding online resources. DISCUSSION: Our results offer precise insights into the needs, use and expectations of people bereaved by suicide regarding online resources. The development of web platforms offering access to reliable information on suicide bereavement and on suicide prevention to peers bereaved by suicide and help to seek counselling are urgently needed.

Current practice and perceptions of safety protocols for the use of intraperitoneal chemotherapy in the operating room: results of the IP-OR international survey.

OBJECTIVES: To assess the risk perception and the uptake of measures preventing environment-related risks in the operating room (OR) during hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: A multicentric, international survey among OR teams in high-volume HIPEC and PIPAC centers: Surgeons (Surg), Scrub nurses (ScrubN), Anesthesiologists (Anest), Anesthesiology nurses (AnesthN), and OR Cleaning staff (CleanS). Scores extended from 0-10 (maximum). RESULTS: Ten centers in six countries participated in the study (response rate 100%). Two hundred and eleven responses from 68 Surg (32%), 49 ScrubN (23%), 45 Anest (21%), 31 AnesthN (15%), and 18 CleanS (9%) were gathered. Individual uptake of protection measures was 51.4%, similar among professions and between HIPEC and PIPAC. Perceived levels of protection were 7.57 vs. 7.17 for PIPAC and HIPEC, respectively (p<0.05), with Anesth scoring the lowest (6.81). Perceived contamination risk was 4.19 for HIPEC vs. 3.5 for PIPAC (p<0.01). Information level was lower for CleanS and Anesth for HIPEC and PIPAC procedures compared to all other responders (6.48 vs. 4.86, and 6.48 vs. 5.67, p<0.01). Willingness to obtain more information was 86%, the highest among CleanS (94%). CONCLUSIONS: Experience with the current practice of safety protocols was similar during HIPEC and PIPAC. The individual uptake of protection measures was rather low. The safety perception was better for PIPAC, but the perceived level of protection remained relatively low. The willingness to obtain more information was high. Intensified, standardized training of all OR team members involved in HIPEC and PIPAC is meaningful.

Implications of Pathologic Findings in Cytoreductive Surgery Specimens on Treatment of Colorectal Peritoneal Metastases: Results of a Prospective Multicentric Study.

BACKGROUND: A surgical peritoneal cancer index of >20 is often used to exclude patients from cytoreductive surgery for colorectal peritoneal metastases. The pathologic peritoneal cancer index in these patients may be <20. OBJECTIVE: The purpose of this study was to compare the pathologic and surgical findings and to look at potential pathologic prognostic factors. DESIGN: This is a prospective observational study including patients undergoing cytoreductive surgery. SETTINGS: The study was carried out at 3 peritoneal surface malignancy centers, 1 in France and 2 in India. PATIENTS: One-hundred patients were included from July 1, 2018, to June 30, 2019. MAIN OUTCOME MEASURES: The pathologic peritoneal cancer index, peritoneal disease distribution, pathologic response to chemotherapy, factors affecting them and their relation with surgical findings, and potential prognostic value were explored. RESULTS: Ninety percent had colonic primaries. Fifty-one percent had left-sided tumors. The median surgical peritoneal cancer index was 4 (range, 0-35). Upper regions were involved in 32% and small bowel regions in 26%, and their involvement increased with a higher peritoneal cancer index (p < 0.001). The median pathologic peritoneal cancer index was 2 (range, 0-27) and was less than the surgical peritoneal cancer index in 57%. A pathologic complete response was obtained in 25%. Patients with pathologic complete response received more antiepidermal growth factor receptor therapy (p = 0.008); more leucovorin, 5-fluorouracil, and oxaliplatin; and folinic acid, fluorouracilirin, irinotecan hydrochloride, and oxaliplatin (p < 0.001). In 7 patients with a surgical peritoneal cancer index of >20, pathologic peritoneal cancer index was <20 in 4 patients. Disease in the primary tumor/anastomotic site was found in ≈80%. LIMITATIONS: Survival outcomes are not available. CONCLUSIONS: Surgical peritoneal cancer index of >20 should not be the sole factor to exclude patients from surgery, especially in responders to systemic therapies. The pathologic peritoneal cancer index, pathologic response to systemic chemotherapy, and disease distribution in the peritoneal cavity should be meticulously documented. Correlation with survival will define their future prognostic value. The primary anastomotic site is a common site for peritoneal disease and should be carefully evaluated in all patients. See Video Abstract at http://links.lww.com/DCR/B490. IMPLICACIONES DE LOS HALLAZGOS PATOLÓGICOS EN MUESTRAS DE CIRUGÍA CITORREDUCTORA EN EL TRATAMIENTO DE METÁSTASIS PERITONEALES COLORRECTALES: RESULTADOS DE UN ESTUDIO PROSPECTIVO MULTICÉNTRICO: Una ICP quirúrgica de >20 se utiliza a menudo para excluir a los pacientes de la cirugía citorreductora por metástasis peritoneales colorrectales. La PCI patológica en estos pacientes puede ser <20.Comparar los hallazgos patológicos y quirúrgicos y observar los posibles factores pronósticos patológicos.Se trata de un estudio observacional prospectivo que incluye a pacientes sometidos a cirugía citorreductora.El estudio se llevó a cabo en tres centros de malignidad de la superficie peritoneal, 1 en Francia y 2 en India.Se incluyeron 100 pacientes desde el 1 de julio de 2018 al 30 de junio de 2019.No hubo intervención terapéutica.Se exploró la ICP patológica, la distribución de la enfermedad peritoneal, la respuesta patológica a la quimioterapia, los factores que la afectan y su relación con los hallazgos quirúrgicos y el valor pronóstico potencial.El noventa por ciento tenía lesiones primarias colónicas. El 51% tenía tumores del lado izquierdo. La mediana de la ICP quirúrgica 4 [0-35]. Las regiones superiores estuvieron involucradas en el 32% y las regiones del intestino delgado en un 26% y su participación aumentó con una ICP más alta (p <0,001). La mediana de la ICP patológica fue 2 [0-27] y fue menor que la ICP quirúrgica en el 57%. Se obtuvo respuesta patológica completa en el 25%. Los pacientes con respuesta patológica completa recibieron más terapia anti-EGFR (p = 0,008) y más FOLFOX y FOLFIRINOX (p <0,001). En 7 pacientes con una ICP quirúrgica de> 20, la ICP patológica fue menor de 20 en 4 pacientes. Se encontró enfermedad en el tumor primario/anastomósis en casi el 80%.Los resultados de supervivencia no están disponibles.La ICP quirúrgica de> 20 no debería ser el único factor para excluir a los pacientes de la cirugía, especialmente en los que responden a las terapias sistémicas. La PCI patológica, la respuesta patológica a la quimioterapia sistémica y la distribución de la enfermedad en la cavidad peritoneal deben documentarse meticulosamente. La correlación con la supervivencia definirá su valor pronóstico futuro. El sitio anastomótico primario es un sitio común de enfermedad peritoneal y debe evaluarse cuidadosamente en todos los pacientes. Consulte Video Resumen en http://links.lww.com/DCR/Bxxx. (Traducción-Dr. Gonzalo Hagerman).

Development of an Online Resource for People Bereaved by Suicide: A Mixed-Method User-Centered Study Protocol.

Introduction: Suicide bereavement is known to be highly distressing and is frequently associated with mental health problems. Despite high-level of need regarding mental and physical health, people bereaved by suicide display low level of help-seeking and perceived support in the aftermath of the loss. The lack of accessibility and reliability of face-to-face counseling resources is notably reported by suicide survivors. Online resources can enhance early access to help and support for people bereaved by suicide. The primary objective of the study is to design and implement an innovative and adaptive online resource for people bereaved by suicide according to their needs and expectation regarding online solutions dedicated to suicide bereavement. Methods: The ESPOIR2S study is a mixed-method user-centered study. ESPOIR2S seeks to build the resource from the perspectives and needs of both people bereaved by suicide and professionals or volunteers working in the field of postvention. The Information System Research (ISR) Framework is used to guide the design of the study through a 3-step research cycle. The structure of the ESPOIR2S study relies on a simultaneous collection of qualitative and quantitative data which will be collected and analyzed during (a) the Relevance cycle through an online questionnaire and focus groups; (b) the Design cycle through focus groups; and (c) and the Rigor cycle through an online questionnaire and semi-structured interviews. The user-centeredness will be ensured by the active participation of people bereaved by suicide, members of associations for bereaved people and professionals of postvention. Discussion: The mixed-method and user-centered design of the ESPOIR2S study will offer an in-depth collection of the needs and expectation of suicide survivors regarding online resources. Through the implementation of an adaptive online solution, we aim to enhance the access to help and support for suicide survivors which are highly correlated with well-being and recovery.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable peritoneal metastasis from gastric cancer.

BACKGROUND: PIPAC is a recent approach with promising results for patients with peritoneal metastasis (PM). We aimed to evaluate survival and postoperative outcome of patients with unresectable PM from gastric origin treated with chemotherapy and PIPAC. METHODS: A retrospective analysis of a prospective maintained PIPAC database was queried for all patients diagnosed with unresectable PM from gastric cancer who underwent PIPAC before 2018. PIPAC with Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 6-week intervals. Outcome criteria were overall survival and adverse events according to (CTCAE) version4.0. RESULTS: One hundred Sixty-three PIPAC were done in 42 consecutive patients. Twenty-two (52%) of the patients were female. Signet-ring cells were observed in 33/42 patients (78.6%). At the first PIPAC, median age was 51.5 years (32-74). Median PCI was 17 (1-39). Twenty (47.6%) patients underwent more than 2 lines of pre-PIPAC chemotherapy. All patients had systemic chemotherapy alternating with PIPAC. Median consecutive PIPAC procedures were 3 (1-12). Overall and major complications (CTCAE - III, IV) occurred in 10 (6.1%) and 5 procedures (3.1%), respectively. Two patients (4.7%) died within 30 days of a PIPAC procedure, one related to small bowel obstruction and a pulmonary embolism for the other. Overall Survival was 19.1 months. Six (14.3%) patients became resectable during treatment and underwent curative intent CRS and HIPEC. CONCLUSIONS: PIPAC with low-dose cisplatin and doxorubicin is safe and feasible in association with systemic chemotherapy for gastric PM. Survival data are encouraging and justify further clinical studies in this indication.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in association with systemic chemotherapy and bevacizumab, evaluation of safety and feasibility. A single center comparative study.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising technic for unresectable peritoneal metastasis (PM). Targeted therapies such as bevacizumab have demonstrated their efficacy in advanced colorectal and ovarian cancer. We aimed to evaluate the feasibility and safety of this bidimensional therapeutic association. METHODS: A prospectively maintained PIPAC database was retrospectively analyzed from December 2015 to March 2018. All patients who underwent PIPAC for unresectable PM were selected. Patients with systemic chemotherapy including bevacizumab (BEVA group) were compared with patients with systemic chemotherapy without bevacizumab (NON-BEVA group). Major morbidity and mortality were analyzed. RESULTS: 134 patients underwent 397 PIPAC in Lyon Sud University Hospital. 26 Patients had 88 PIPAC in the BEVA group were compared to 108 patients who had 309 PIPAC in the NON-BEVA group. Patients in the BEVA group demonstrated a higher Peritoneal Cancer Index (PCI 20 vs. 16, p < 0.001). There was no statistical difference in overall 30-day morbidity (BEVA: 13 (14.8%) vs NON-BEVA: 29 (9.4%); p = 0.147). There was no statistical difference for grade III-IV complications (BEVA: 4 (4.5%) vs NON-BEVA 10 (3.2%); P = 0.521). Major complications from BEVA group were as follow, 2 bowel obstructions, one hematoma and one severe hypersensitivity reaction to platinum compound. There was no 30-day mortality in the BEVA group compared to 6 (5.5%) mortality in the NON-BEVA group. CONCLUSION: PIPAC associated with bevacizumab is feasible, safe and well tolerated. The potential oncologic benefit of the concomitant use of bevacizumab and PIPAC remains to be evaluated.

Unresectable peritoneal metastasis treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC) leading to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: PIPAC is a recent method of intraperitoneal chemotherapy. The aim of this study was to describe the clinical characteristics of the patients who became amenable to CRS & HIPEC after PIPAC treatment. METHODS: All patients diagnosed with unresectable PM who became resectable throughout PIPAC treatment were included. Outcome criteria were adverse events following PIPAC procedure and rate of secondary CRS and HIPEC. RESULTS: Four hundred thirty-seven PIPAC were done in 146 consecutive patients. Among them, 26 patients (17.8%) who underwent 76 PIPAC were scheduled for CRS and HIPEC after reduction of the peritoneal burden. PM were from gastric, peritoneal mesothelioma, ovarian, colorectal and small bowel in 13, 7, 4, 1 and 1 patients, respectively. At the time of the first PIPAC, median age was 58.6 years (32-76.3). Median PCI was 16 (1-39). All patients had systemic chemotherapy in between PIPAC session. Median consecutive PIPAC procedure was 3 (1-8). Complications occurred in 3 PIPAC session (4%) and there was no major complication (CTCAE III or higher). Complete CRS and HIPEC was achieved in 21 patients of the 26 scheduled (14.4%). The remaining 5 patients were considered unresectable at the exploratory laparotomy. Among patients who underwent CRS and HIPEC, with median follow-up of 7 (1-26) months, 14 patients (66.7%) were alive without recurrence, 2 patients (9.5%) were alive with recurrence and 5 patients (23.8%) died. CONCLUSIONS: Complete CRS and HIPEC can be achieved in strictly selected patient with unresectable PM at diagnosis after repeated PIPAC session with palliative intent.

Prognostic impact of combined progression index based on peritoneal grading regression score and peritoneal cytology in peritoneal metastasis.

AIMS: The peritoneal regression grading score (PRGS) and peritoneal cytology (PC) assess response to chemotherapy in peritoneal metastasis (PM) in a setting of palliative treatment by pressurized intraperitoneal aerosol chemotherapy (PIPAC). Progression has been defined as an increase of PRGS between first and third PIPAC procedures (iPRGS). iPRGSand positive peritoneal cytology were not associated with prognostic impact. These results may be explained by a lack of statistical power. Also, it is not known whether the mean or the highest PRGS among taken peritoneal biopsies bears the highest clinical value. We therefore conducted the largest prospective study to investigate the prognostic impact of PGRS, PC, and their combination, designated as combined progression index (CPI). METHODS AND RESULTS: Patients with PM who underwent >3 PIPAC (n = 112) between December 2016 and February 2019 were prospectively included. A significant difference in OS and PFS according to CPI (used highest value of PRGS) was found (OS: CPI-, 83.3, 95% CI [49.8; NA] vs. CPI+, 48.1, 95% CI [38.5; 66.4] months; and PFS (respectively, 59.7, 95% CI [43.0; 96.0] vs. 33.7, 95% CI [30.4; 44.2] months). PRGS or PC had no independent prognostic impact. CPI+ was an independent predictor of worse prognosis, in OS (HR = 5.24, 95% CI [2.07; 13.26]), and PFS (HR = 4.41, 95% CI [1.40; 13.88]). CONCLUSIONS: The CPI based on highest PRGS and PC was found to be independently associated with a worse prognosis for OS and for PFS in the setting of peritoneal metastasis. These results indicate that it should be of interest to systematically take peritoneal fluid for cytological examination and to implement the CPI in the therapeutic decision-making process in the context of PIPAC.

Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications.

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.

Unexpected discrepancies in hospital administrative databases can impact the accuracy of monitoring thyroid surgery outcomes in France.

OBJECTIVE: To determine the validity of hospital administrative databases compared to prospective collection of medical data assessing thyroid surgery complications. BACKGROUND: Administrative data are increasingly used to track surgical outcomes. METHODS: All patients undergoing thyroid surgery at three French university hospitals between April 2008 and April 2009 were prospectively included. Using diagnosis and procedural codes from hospital administrative database, we designed three indicators for measuring complications of thyroid surgery: recurrent laryngeal nerve palsy, postoperative hypoparathyroidism, and postoperative hemorrhage. Gold standard was obtained from a prospective collection of medical data after systematically screening each patient for the above-mentioned complications. Their ability to monitor surgical outcomes over time within individual hospitals was estimated using control charts. Spatial comparison between hospitals was performed by funnel plots. RESULTS: A total of 1909 patients were included. Complication rates extracted from administrative data were significantly lower compared to medical data (nerve palsy 2.4% vs. 6.7%, hypoparathyroidism 10.6% vs. 22.3%, p<0.0001). Indicator sensitivity was 30.4% for nerve palsy, 45.4% for hypoparathyroidism and 71.4% for postoperative hemorrhage. Corresponding positive predictive values were 84.4%, 95.1% and 68.2%. In two of the three hospitals, administrative data were not able to track temporal variations in complications rates. Regarding inter-hospital comparisons, 2 out of 3 hospitals were considered outliers according to administrative data despite having an average performance based on medical data. CONCLUSIONS: The ability of indicators extracted from administrative databases to measure thyroid surgery outcomes depends on the quality of underlying data coding. Validation in every center should be a prerequisite before implementing such metrics for tracking performance.

Correction to: Does Surgery Without Lugol's Solution Pretreatment for Graves' Disease Increase Surgical Morbidity?

In the original article, Mathieu Bonal's last name was spelled incorrectly. It is correct as reflected here. The original article has also been updated.

Does Surgery Without Lugol's Solution Pretreatment for Graves' Disease Increase Surgical Morbidity?

BACKGROUND: Total thyroidectomy can be performed for Graves' disease after a euthyroid state is achieved using inhibitors of thyroid hormone synthesis (thioamides). However, hypervascularization of the thyroid gland is associated with increased hemorrhage risk, in addition to complicating identification of the recurrent laryngeal nerve and parathyroid gland. Saturated iodine solution (Lugol's solution) has been recommended to reduce thyroid gland hypervascularization and intraoperative blood loss, although this approach is not used at our center based on our experience that it induces thyroid firmness and potentially hypoparathyroidism. METHODS: This retrospective single-center study evaluated patients who underwent total thyroidectomy for Graves' disease between November 2010 and November 2015. The rates of various complications at our center were compared to those from the literature (e.g., cervical hematoma, hypocalcemia, and recurrent laryngeal nerve palsy). RESULTS: Three hundred and eighty consecutive patients underwent total thyroidectomy without preoperative Lugol's solution (311 women [81.84%] and 69 men [18.16%], mean age 43.41 years). No postoperative deaths were reported, although 30 patients (7.89%) experienced recurrent laryngeal nerve palsy and 9 patients experienced permanent injuries (2.37%). Hypoparathyroidism was experienced by 87 patients (25.53%) and 14 patients experienced permanent hypoparathyroidism (3.68%). Four patients required reoperation for cervical hematoma (1.05%; 2 deep and 2 superficial hematomas). CONCLUSION: Despite the recommendation of iodine pretreatment, few of our non-pretreated patients experienced permanent nerve injury (2.37%) or permanent hypoparathyroidism (3.68%). These results are comparable to the outcomes from the literature. Randomized controlled trials are needed to determine whether iodine pretreatment is necessary before surgery for Graves' disease.

Surgery for recurrent adrenocortical carcinoma: A multicenter retrospective study.

BACKGROUND: Adrenocortical carcinoma is a rare neoplasm with a high rate of recurrence. We studied the impact of surgery on the survival in recurrent adrenocortical carcinoma patients. METHODS: We performed a retrospective review of patients with recurrent adrenocortical carcinoma, managed in 5 French University Hospitals between 1980 and 2014. We compared surgery and medical management for ACC recurrence. RESULTS: Fifty-nine patients were included, 46 of whom had an initial R0 resection. Twenty-nine patients underwent reoperation for recurrence, while 30 had nonoperative treatments. Operated patients had a greater median overall survival after recurrence than nonoperated patients (91 vs 15 months; P < .001). Patients operated on for local or distant recurrence had similar overall survival (110 vs 91 months; P = .81). In nonoperated patients, types of medical managements did not impact survival. Surgery for recurrence (P = .037) and a disease-free interval between initial resection and recurrence >12 months (P = .059) were both prognostic factors for improved survival, whereas age, stage, and tumor size (P ≥ .2 each) were not. A Ki67 <25% tended to be associated with better overall survival (P = .051). CONCLUSION: Both surgery for recurrence and disease-free interval between the initial resection of an adrenocortical carcinoma and recurrence >12 months are associated with better overall survival.

Cardiac fibroblasts regulate sympathetic nerve sprouting and neurocardiac synapse stability.

Sympathetic nervous system (SNS) plays a key role in cardiac homeostasis and its deregulations always associate with bad clinical outcomes. To date, little is known about molecular mechanisms regulating cardiac sympathetic innervation. The aim of the study was to determine the role of fibroblasts in heart sympathetic innervation. RT-qPCR and western-blots analysis performed in cardiomyocytes and fibroblasts isolated from healthy adult rat hearts revealed that Pro-Nerve growth factor (NGF) and pro-differentiating mature NGF were the most abundant neurotrophins expressed in cardiac fibroblasts while barely detectable in cardiomyocytes. When cultured with cardiac fibroblasts or fibroblast-conditioned medium, PC12 cells differentiated into/sympathetic-like neurons expressing axonal marker Tau-1 at neurites in contact with cardiomyocytes. This was prevented by anti-NGF blocking antibodies suggesting a paracrine action of NGF secreted by fibroblasts. When co-cultured with cardiomyocytes to mimic neurocardiac synapse, differentiated PC12 cells exhibited enhanced norepinephrine secretion as quantified by HPLC compared to PC12 cultured alone while co-culture with fibroblasts had no effect. However, when supplemented to PC12-cardiomyocytes co-culture, fibroblasts allowed long-term survival of the neurocardiac synapse. Activated fibroblasts (myofibroblasts) isolated from myocardial infarction rat hearts exhibited significantly higher mature NGF expression than normal fibroblasts and also promoted PC12 cells differentiation. Within the ischemic area lacking cardiomyocytes and neurocardiac synapses, tyrosine hydroxylase immunoreactivity was increased and associated with local anarchical and immature sympathetic hyperinnervation but tissue norepinephrine content was similar to that of normal cardiac tissue, suggesting depressed sympathetic function. Collectively, these findings demonstrate for the first time that fibroblasts are essential for the setting of cardiac sympathetic innervation and neurocardiac synapse stability. They also suggest that neurocardiac synapse functionality relies on a triptych with tight interaction between sympathetic nerve endings, cardiomyocytes and fibroblasts. Deregulations of this triptych may be involved in pathophysiology of cardiac diseases.