Impairment of Renal and Hematopoietic Stem/Progenitor Cell Compartments in Frailty Syndrome: Link With Oxidative Stress, Plasma Cytokine Profiles, and Nuclear DNA Damage.

Frailty is an age-related syndrome that drives multiple physiological system impairments in some older adults, and its pathophysiological mechanisms remain unclear. We evaluated whether frailty-related biological processes could impair stem cell compartments, specifically the renal stem compartment, given that kidney dysfunctions are frequent in frailty. A well-characterized in vitro nephrosphere model of human adult renal stem/progenitor cells has been instrumental to and was appropriate for verifying this hypothesis in our current research. Evaluating the effects of plasma from older individuals with frailty (frail plasma) on allogeneic renal stem/progenitor cells, we showed significant functional impairment and nuclear DNA damage in the treated cells of the renal stem compartment. The analysis of the frail plasma revealed mitochondrial functional impairment associated with the activation of oxidative stress and a unique inflammatory mediator profile in frail individuals. In addition, the plasma of frail subjects also contained the highest percentage of DNA-damaged autologous circulating hematopoietic progenitor/stem cells. The integration of both molecular and functional data obtained allowed us to discern patterns associated with frailty status, irrespective of the comorbidities present in the frail individuals. The data obtained converged toward biological conditions that in frailty caused renal and hematopoietic impairment of stem cells, highlighting the possibility of concomitant exhaustion of several stem compartments.

Learning curve of laparoscopic cholecystectomy: a risk-adjusted cumulative summation (RA-CUSUM) analysis of six general surgery residents.

BACKGROUND: Laparoscopic cholecystectomy (LapC) is one of the most frequently performed surgical procedures worldwide. Reaching technical competency in performing LapC is considered one essential task for young surgeons. Investigating the learning curve for LapC (LC-LapC) may provide important information regarding the learning process and guide the training pathway of residents, improving educational outcomes. The present study aimed to investigate LC-LapC among general surgery residents (GSRs). METHODS: Operative surgical reports of consecutive patients undergoing LapC performed by GSRs attending the General Surgery Residency Program at the University of Milan were analysed. Data on patient- and surgery-related variables were obtained from the ICD-9-CM diagnosis codes and gathered. A multidimensional assessment of the LC was performed through Cumulative Sum (CUSUM) and Risk-Adjusted (RA)-CUSUM analysis. RESULTS: 340 patients operated by 6 GSRs were collected. The CUSUM and RA-CUSUM graphs based on surgical failures allowed to distinguish two defined phases for all GSRs: an initial phase ending at the peak, so-called learning phase, followed by a phase in which there was a significant decrease in failure incidence, so-called proficiency phase. The learning phase was completed for all GSRs at most within 25 procedures, but the trend of the curves and the number of procedures needed to achieve technical competency varied among operators ranging between 7 and 25. CONCLUSIONS: The present study suggested that at most 25 procedures might be sufficient to acquire technical competency in LapC. The variability in the number of procedures needed to complete the LC, ranging between 7 and 25, could be due to the heterogeneous scenarios in which LapC was performed, and deserves to be investigated through a prospective study involving a larger number of GSRs and institutions.

Multidimensional evaluation of the learning curve for totally laparoscopic pancreaticoduodenectomy: a risk-adjusted cumulative summation analysis.

INTRODUCTION: Laparoscopic pancreaticoduodenectomy (LPD) is a challenging procedure. We investigated the learning curve (LC) for LPD with a multidimensional analysis. METHODS: Data of patients undergoing LPD between 2017 and 2021, operated by a single surgeon, were considered. A multidimensional assessment of the LC was performed through Cumulative Sum (CUSUM) and Risk-Adjusted (RA)-CUSUM analysis. RESULTS: 113 patients were selected. Rates of conversion, overall postoperative complication, severe complication and mortality were 4%, 53%, 29% and 4%, respectively. RA-CUSUM analysis showed a LC with three phases: competency (procedures 1-51), proficiency (procedures 52-94), and mastery (after procedure 94). Operative time was lower in both phase two (588.17 vs 541.13 min, p = 0.001) and three (534.72 vs 541.13 min, p = 0.004) with respect to phase one. Severe complication rate was lower in mastery as compared to competency phase (42% vs 6%, p = 0.005). During mastery phase a greater number of lymph nodes was harvested in comparison to proficiency phase. CONCLUSIONS: According to our LC analysis, 52 procedures were required to achieve technical competency in LPD. Mastery, which corresponded to a reduction in operative time and surgical failures, was acquired after 94 procedures.

Multidimensional evaluation of the learning curve for laparoscopic complete mesocolic excision for right colon cancer: a risk-adjusted cumulative summation analysis.

AIM: Despite the suggested potential benefit of complete mesocolic excision (CME) for right-sided colon cancer (RCC) for patient survival, concerns about its safety and feasibility have contributed to delayed acceptance of the procedure, especially when performed by a minimally invasive approach. Thus, the aim of this work was to evaluate the actual learning curve (LC) of laparoscopic CME for experienced colorectal surgeons. METHOD: Prospectively collected data for consecutive patients undergoing laparoscopic CME for RCC between October 2015 and January 2021 at our institution, operated on by experienced surgeons, were analysed. A multidimensional assessment of the LC was performed through cumulative sum (CUSUM) and risk-adjusted (RA) CUSUM analysis. RESULTS: Two hundred and two patients operated by on by three surgeons were considered. The CUSUM graphs based on operating time showed one peak of the curve between 17 and 27 cases. The CUSUM graphs based on surgical failure showed one peak of the curve between 20 and 24 cases The RA-CUSUM curve also showed one preeminent peak at 24-33 cases. Based on the CUSUM and RA-CUSUM analyses all the surgeons reached proficiency in 24-33 cases. CONCLUSIONS: Our study showed that an experienced minimally invasive colorectal surgeon acquires proficiency in laparoscopic CME for RCC after performing 24-33 cases.