Safety and efficacy analysis of neoadjuvant pertuzumab, trastuzumab and standard chemotherapy for HER2-positive early breast cancer: real-world data from NeoPowER study.

BACKGROUND: The addition of pertuzumab (P) to trastuzumab (H) and standard chemotherapy (CT) as neoadjuvant treatment (NaT) for patients with HER2 + breast cancer (BC), has shown to increase the pathological complete response (pCR) rate, without main safety concerns. The aim of NeoPowER trial is to evaluate safety and efficacy of P + H + CT in a real-world population. METHODS: We retrospectively reviewed the medical records of stage II-III, HER2 + BC patients treated with NaT: who received P + H + CT (neopower group) in 5 Emilia Romagna institutions were compared with an historical group who received H + CT (control group). The primary endpoint was the safety, secondary endpoints were pCR rate, DRFS and OS and their correlation to NaT and other potential variables. RESULTS: 260 patients were included, 48% received P + H + CT, of whom 44% was given anthraciclynes as part of CT, compared to 83% in the control group. The toxicity profile was similar, excluding diarrhea more frequent in the neopower group (20% vs. 9%). Three patients experienced significant reductions in left ventricular ejection fraction (LVEF), all receiving anthracyclines. The pCR rate was 46% (P + H + CT) and 40% (H + CT) (p = 0.39). The addition of P had statistically correlation with pCR only in the patients receiving anthra-free regimens (OR = 3.05,p = 0.047). Preoperative use of anthracyclines (OR = 1.81,p = 0.03) and duration of NaT (OR = 1.18,p = 0.02) were statistically related to pCR. 12/21 distant-relapse events and 14/17 deaths occurred in the control group. Patients who achieve pCR had a significant increase in DRFS (HR = 0.23,p = 0.009). CONCLUSIONS: Adding neoadjuvant P to H and CT is safe. With the exception of diarrhea, rate of adverse events of grade > 2 did not differ between the two groups. P did not increase the cardiotoxicity when added to H + CT, nevertheless in our population all cardiac events occurred in patients who received anthracycline-containing regimens. Not statistically significant, higher pCR rate is achievable in patients receiving neoadjuvant P + H + CT. The study did not show a statistically significant correlation between the addition of P and long-term outcomes.

Small deviations between planned and performed bone cuts using a CT-based robotic-arm-assisted total knee arthroplasty system.

PURPOSE: Computed tomography (CT)-based robotic system for total knee arthroplasty (TKA) has shown improved accuracy compared to conventional. This study was designed to (1) confirm the accuracy of the robotic system in achieving the plan and (2) establish the alignment and positioning deviation between final components and planning, by measuring the discrepancy between final implant alignment and the corresponding planned cut. METHODS: Ninety-six cementless robotic-arm assisted (RA) TKAs were assessed. Bone resections were performed using the haptically controlled robotic arm. Alignment in the coronal and sagittal plane and resection depth of the distal femoral and proximal tibial cuts were recorded with a navigation planar probe. After final components were impacted, the probe was positioned on each implant surface to determine its alignment and positioning. RESULTS: The mean tibial resections and implanted tibial component's positioning were 0.4 mm (standard deviation, SD: 0.6) and 0.9 mm (SD: 0.8), respectively, higher than planned (p < 0.01). The tibial sagittal cut had 19/96 cases (19.8%) of ±1° outliers from plan. In 40/96 cases (41.7%), the tibial component was more prominent than planned of more than 1 mm. The mean femoral resections and impacted femoral component's positioning was 0.1 mm (SD: 0.8) and 0.2 mm (SD: 0.7), respectively, higher than planned. In 23/96 cases (24.0%), the femoral sagittal cut and femoral component coronal alignment deviated more than ±1° from plan. CONCLUSIONS: The computed tomography-based robotic-assisted TKA system showed good accuracy regarding bone preparation and component's positioning relative to the planning. Cementless tibial component impaction resulted in the most deviation from plan, with a large proportion of cases resulting in being more prominent than planned. LEVEL OF EVIDENCE: Level III.

Image-based robotic-arm assisted unicompartmental knee arthroplasty provides high survival and good-to-excellent clinical outcomes at minimum 10 years follow-up.

PURPOSE: The purpose of the present study was to determine the incidence of revision and report on clinical outcomes at a minimum of 10 years follow-up in patients who had received a medial unicompartmental knee arthroplasty (UKA) with an three-dimensional image-based robotic system. METHODS: A total of 239 patients (247 knees), who underwent medial robotic-arm assisted (RA)-UKA at a single center between April 2011 and June 2013, were assessed. The mean age at surgery was 67.0 years (SD 8.4). Post-operatively, patients were administered the Forgotten Joint Score-12 (FJS-12) and asked about their satisfaction (from 1 to 5). Post-operative complications were recorded. Failure mechanisms, revisions and reoperations were collected. Kaplan-Meier survival curves were calculated, considering revision as the event of interest. RESULTS: A total of 188 patients (196 knees) were assessed at a mean follow-up of 11.1 years (SD 0.5, range 10.0-11.9), resulting in a 79.4% follow-up rate. Seven RA-UKA underwent revision, resulting in a survivorship rate of 96.4% (CI 94.6%-99.2%). Causes of revision included aseptic loosening (2 cases), infection (1 case), post-traumatic (1 case), and unexplained pain (3 cases). The mean FJS-12 and satisfaction were 82.2 (SD 23.9) and 4.4 (SD 0.9), respectively. Majority of cases (174/196, 88.8%) attained the Patient Acceptable Symptoms State (PASS, FJS-12 > 40.63). Male subjects had a higher probability of attaining a "forgotten joint" (p < 0.001) and high satisfaction (equal to 5, p < 0.05), when compared to females. CONCLUSIONS: Three-dimensional image-based RA-UKA demonstrated high implant survivorship and good-to-excellent clinical outcomes at minimum 10 years follow-up. Pain of unknown origin represented the most common reason for RA-UKA revision. LEVEL OF EVIDENCE: III.

No difference in clinical outcomes between functionally aligned cruciate-retaining and posterior-stabilized robotic-assisted total knee arthroplasty.

PURPOSE: To compare the clinical outcomes of subjects undergoing primary robotic-assisted total knee arthroplasty (RA-TKA), following functional alignment (FA) principles, with cruciate-retaining (CR) or posterior-stabilized (PS) bearing designs, at a minimum of 24 months of follow-up. METHODS: This observational, retrospective study included 167 consecutive patients undergoing RA-TKA with cemented PS and cementless CR implants performed with a CT-base robotic-arm assisted system (Mako, Stryker), following FA principles, between 2017 and 2020. Patients were followed up with a clinical and radiographic assessment and were administered the Forgotten Joint Score-12 (FJS-12), Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR), and the 5-level Likert scale (5-LLS). RESULTS: Three TKA revisions were performed (2 PS, 1 CR); therefore, a total of 164 knees with a mean age of 71.7 years (SD 8.9) were considered (80 cemented PS; 84 cementless CR). No statistically significant differences were recorded between study groups relative to FJS-12, KOOS-JR, and 5-LLS at a minimum of two year follow-up (FJS-12 89.3 ± 9.2 vs 87.5 ± 12.8, p-value 0.46; KOOS-JR 88.8 ± 10.0 vs 86.7 ± 14.0, p-value 0.31; 5-LLS 4.5 ± 0.7 vs 4.5 ± 0.8, p-value 0.34). CONCLUSION: No significant outcome differences were reported between patients undergoing PS and CR RA-TKA at a minimum of two year follow-up. RA-TKA achieves excellent clinical results and high satisfaction scores, regardless of the implant design used.

High return to sport rate in patients undergoing image-based robotic arm assisted unicompartmental knee arthroplasty.

INTRODUCTION: This study was aimed to assess the return to sport (RTS) rate in patients who underwent CT-based robotic-assisted unicompartmental knee arthroplasty (RA-UKA) and to evaluate the clinical performance and the assocition between patients' sport activity levels and Patient Reported Outcome Measures after surgery. MATERIALS AND METHODS: This retrospective study included 218 patients undergoing medial RA-UKA with fixed-bearing implants, performed at a single center between 2014 and 2019. Patients were allocated into two groups based on sport's practice and were administered the University of California, Los Angeles (UCLA) activity scale, Forgotten Joint Score-12 (FJS-12), Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) and the 5-Level Likert Scale. RESULTS: A total of 136 patients were included for assessment. The overall RTS rate after surgery was 93.1%. Six subjects who did not practice sport preoperatively, were able to start sport activities after surgery and all patients performing sports preoperatively, returned to same activity level. The mean UCLA and FJS-12 scores in the group of patients practicing sports were significantly higher than in the no-sport group (p < 0.001 and p < 0.05, respectively). Patients who practiced sports were more likely to attain higher FJS-12 and UCLA scores than those who were not performing physical activity. CONCLUSIONS: Patients undergoing RA-UKA showed a 93.1% RTS rate after surgery. Differences were detected in terms of postoperative UCLA and FJS-12 scores between patients who performed and who did not practice sport activities after surgery. High levels of postoperative UCLA scores were associated with higher KOOS-JR and patients' satisfaction.

Role of Body Composition in Patients with Resectable Pancreatic Cancer.

This study investigates the role of body composition parameters in patients with pancreatic cancer undergoing surgical treatment. The research involved 88 patients diagnosed with pancreatic cancer who underwent surgery at the Modena Cancer Center between June 2015 and October 2023. Body composition parameters were obtained from CT scans performed before and after surgery. The percentage of sarcopenic patients at the time of diagnosis of pancreatic cancer is 56.82%. Of the patients who died between the first and second CT evaluated, 58% were sarcopenic, thus confirming the role of sarcopenia on outcome. The study found that all body composition parameters (TAMA, SMI, VFI, and SFI) demonstrated a trend towards reduction between two examinations, indicating an overall depletion in muscle and adipose tissue. We then evaluated the relationships between fat-related parameters (VFI, SFI and VSR) and survival outcomes: overall survival and progression-free survival. Cox univariate regression model show significant parameter related to outcomes was adipose tissue, specifically VFI. The study found that higher VFI levels were associated with greater survival rates. This research holds promise for advancing our understanding of the link between body composition and the prognosis of pancreatic cancer patients.

Cognitive, behavioral and socio-communication skills as predictors of response to Early Start Denver Model: a prospective study in 32 young children with Autism Spectrum Disorder.

Introduction: The effectiveness of early interventions in young autistic children is well established, but there is great interindividual variability in treatment response. Predictors of response to naturalistic developmental behavioral interventions (NDBI), like the Early Start Denver Model (ESDM), are needed. Methods: We conducted an exploratory study to prospectively seek predictors of response in 32 young children treated with ESDM after receiving an ASD diagnosis. All children were less than 39 months old (mean age: 29.7 mo), and received individualized ESDM for nine months. Tests were administered at the beginning, after 4 months, and at the end of treatment. Results: Four children (12.5%) were "strong responders", 8 children (25.0%) were "moderate responders", and 20 children (62.5%) were "poor responders". A more favorable response to ESDM was significantly predicted by higher PEP-3 Expressive Language, Receptive Language, Cognitive Verbal/Preverbal, Visuo-Motor Imitation scores, higher GMDS-ER Personal/Social, and VABS-II Communication scores, by lower ADI-R C restricted/stereotypic behaviors, and by joint attention level. Discussion: Most predictors showed a linear association with increasing response to ESDM, but GMDS-ER Personal-Social and joint attention level predicted strong response, while PEP-3 receptive language equally predicted moderate or strong response. Although larger samples will be necessary to reach definitive conclusions, in conjunction with prior reports our findings begin providing information able to assist clinicians in choosing the most appropriate treatment program for young autistic children.

Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants.

BACKGROUND: There are wide variations in antibiotic use in neonatal intensive care units (NICUs). Limited data are available on antimicrobial stewardship (AS) programs and long-term maintenance of AS interventions in preterm very-low-birth-weight (VLBW) infants. METHODS: We extended a single-centre observational study carried out in an Italian NICU. Three periods were compared: I. "baseline" (2011-2012), II. "intervention" (2016-2017), and III. "maintenance" (2020-2021). Intensive training of medical and nursing staff on AS occurred between periods I and II. AS protocols and algorithms were maintained and implemented between periods II and III. RESULTS: There were 111, 119, and 100 VLBW infants in periods I, II, and III, respectively. In the "intervention period", there was a reduction in antibiotic use, reported as days of antibiotic therapy per 1000 patient days (215 vs. 302, p < 0.01). In the "maintenance period", the number of culture-proven sepsis increased. Nevertheless, antibiotic exposure of uninfected VLBW infants was lower, while no sepsis-related deaths occurred. Our restriction was mostly directed at shortening antibiotic regimens with a policy of 48 h rule-out sepsis (median days of early empiric antibiotics: 6 vs. 3 vs. 2 in periods I, II, and III, respectively, p < 0.001). Moreover, antibiotics administered for so-called culture-negative sepsis were reduced (22% vs. 11% vs. 6%, p = 0.002), especially in infants with a birth weight between 1000 and 1499 g. CONCLUSIONS: AS is feasible in preterm VLBW infants, and antibiotic use can be safely reduced. AS interventions, namely, the shortening of antibiotic courses in uninfected infants, can be sustained over time with periodic clinical audits and daily discussion of antimicrobial therapies among staff members.

Effectiveness of patients' involvement in a medical and nursing pain education programme: a protocol for an open-label randomised controlled trial including qualitative data.

INTRODUCTION: Pain is a multidimensional experience that varies among individuals and has a significant impact on their health. A biopsychosocial approach is recommended for effective pain management; however, health professionals' education is weak on this issue. Patient involvement is a promising didactic methodology in developing a more holistic perspective, however there is a lack of reliable evidence on this topic. The aim of the present study is to evaluate the effectiveness of patient involvement in pain education in undergraduate medicine and nursing students. METHODS AND ANALYSIS: An open-label randomised controlled trial including qualitative data will be conducted. After an introductory lesson, each student will be randomly assigned to the intervention group, which includes an educational session conducted by a patient-partner along with an educator, or to the control group in which the session is exclusively conducted by an educator. Both sessions will be carried out according to the Case-Based Learning approach. Primary outcomes will be students' knowledge, attitudes, opinions and beliefs about pain management, whereas the secondary outcome will be students' satisfaction. The Pain Knowledge and Attitudes (PAK) and Chronic Pain Myth Scale (CPMS) will be administered preintervention and postintervention to measure primary outcomes. Students' satisfaction will be measured by a questionnaire at the end of the session. Two focus groups will be conducted to evaluate non-quantifiable aspects of learning. ETHICS AND DISSEMINATION: The protocol of this study was approved by the independent Area Vasta Emilia Nord ethics committee.Adherence to The Declaration of Helsinki and Good Clinical Practice will ensure that the rights, safety and well-being of the participants in the study are safeguarded, as well as data reliability. The results will be disseminated through scientific publications and used to improve the educational offer. A version of the anonymised data set will be released for public access. TRIAL REGISTRATION: Trial was not registered on ClinicalTrials.gov as the interventions being compared only concern educational programmes and the outcomes considered do not refer to any clinical dimension.

Impact of Nutritional Status on Postoperative Outcomes in Cancer Patients following Elective Pancreatic Surgery.

BACKGROUND: Pancreatic surgery has been associated with important postoperative morbidity, mortality and prolonged length of hospital stay. In pancreatic surgery, the effect of poor preoperative nutritional status and muscle wasting on postsurgery clinical outcomes still remains unclear and controversial. MATERIALS AND METHODS: A total of 103 consecutive patients with histologically proven carcinoma undergoing elective pancreatic surgery from June 2015 through to July 2020 were included and retrospectively studied. A multidimensional nutritional assessment was performed before elective surgery as required by the local clinical pathway. Clinical and nutritional data were collected in a medical database at diagnosis and after surgery. RESULTS: In the multivariable analysis, body mass index (OR 1.25, 95% CI 1.04-1.59, p = 0.039) and weight loss (OR 1.16, 95% CI 1.06-1.29, p = 0.004) were associated with Clavien score I-II; weight loss (OR 1.13, 95% CI 1.02-1.27, p = 0.027) affected postsurgery morbidity/mortality, and reduced muscle mass was identified as an independent, prognostic factor for postsurgery digestive hemorrhages (OR 0.10, 95% CI 0.01 0.72, p = 0.03) and Clavien score I-II (OR 7.43, 95% CI 1.53-44.88, p = 0.018). No association was identified between nutritional status parameters before surgery and length of hospital stay, 30 days reintervention, 30 days readmission, pancreatic fistula, biliary fistula, Clavien score III-IV, Clavien score V and delayed gastric emptying. CONCLUSIONS: An impaired nutritional status before pancreatic surgery affects many postoperative outcomes. Assessment of nutritional status should be part of routine preoperative procedures in order to achieve early and appropriate nutritional support in pancreatic cancer patients. Further studies are needed to better understand the effect of preoperative nutritional therapy on short-term clinical outcomes in patients undergoing pancreatic elective surgery.

"It's All COVID's Fault!": Symptoms of Distress among Workers in an Italian General Hospital during the Pandemic.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, healthcare workers (HCWs) have been faced with specific stressors endangering their physical and mental health and their functioning. This study aimed to assess the short-term psychological health of a sample of Italian HCWs and the related influencing factors. In particular, the study focused on the differences related to HCWs' gender and to having been directly in charge of COVID-19 patients or not. METHODS: An online survey was administered to the whole staff of the Modena General University Hospital three months after the onset of the pandemic, in 2020. Demographic data and changes in working and living conditions related to COVID-19 were collected; mental health status was assessed by the Depression, Anxiety and Stress Scale (DASS-21) and the Impact of Event Scale-Revised (IES-R). RESULTS: 1172 out of 4788 members returned the survey (response rate = 24.5%), the male/female ratio was 30/70%. Clinically significant symptoms assessed according to the DASS-21 emerged among 21.0% of the respondents for depression, 22.5% for anxiety and 27.0% for stress. Symptoms suggestive of a traumatic reaction were reported by 19.0% of the sample. Symptoms of psychological distress were statistically associated with female gender, job role, ward, changes in lifestyle, whereas first-line work with COVID-19 patients was statistically associated with more stress symptoms. HCWs reported a significant level of psychological distress that could reach severe clinical significance and impact dramatically their quality of life and functioning. CONCLUSIONS: Considering the persistence of the international emergency, effective strategies to anticipate, recognize and address distress in HCWs are essential, also because they may impact the organization and effectiveness of healthcare systems.

Escherichia coli Is Overtaking Group B Streptococcus in Early-Onset Neonatal Sepsis.

The widespread use of intrapartum antibiotic prophylaxis (IAP) to prevent group B streptococcus (GBS) early-onset sepsis (EOS) is changing the epidemiology of EOS. Italian prospective area-based surveillance data (from 1 January 2016 to 31 December 2020) were used, from which we identified 64 cases of culture-proven EOS (E. coli, n = 39; GBS, n = 25) among 159,898 live births (annual incidence rates of 0.24 and 0.16 per 1000, respectively). Approximately 10% of E. coli isolates were resistant to both gentamicin and ampicillin. Five neonates died; among them, four were born very pre-term (E. coli, n = 3; GBS, n = 1) and one was born full-term (E. coli, n = 1). After adjustment for gestational age, IAP-exposed neonates had ≥95% lower risk of death, as compared to IAP-unexposed neonates, both in the whole cohort (OR 0.04, 95% CI 0.00-0.70; p = 0.03) and in the E. coli EOS cohort (OR 0.05, 95% CI 0.00-0.88; p = 0.04). In multi-variable logistic regression analysis, IAP was inversely associated with severe disease (OR = 0.12, 95% CI 0.02-0.76; p = 0.03). E. coli is now the leading pathogen in neonatal EOS, and its incidence is close to that of GBS in full-term neonates. IAP reduces the risk of severe disease and death. Importantly, approximately 10% of E. coli isolates causing EOS were found to be resistant to typical first-line antibiotics.