Evaluation of a Commercial Rapid Molecular Point-of-Care Assay for Differential Diagnosis Between SARS-CoV-2 and Flu A/B Infections in a Pediatric Setting.

Given the ongoing COVID-19 pandemic, there is a need to identify SARS-CoV-2 and to differentiate it from other respiratory viral infections, especially influenza A and B, in various critical settings. Since their introduction, the use of rapid antigen tests has spread worldwide, but there is variability in their diagnostic accuracy. In the present study, we evaluated the clinical performance of the ID NOW™ COVID-19 2.0, a molecular point-of-care test (POCT) based on enzymatic isothermal amplification for the differential diagnosis of SARS-CoV-2 and influenza A/B in a pediatric emergency setting. A cohort of pediatric patients admitted between December 2022 and February 2023 were simultaneously tested with the POCT and standard laboratory molecular assay. Our findings showed high negative agreement of the POCT assay across the different age groups for SARS-CoV-2, influenza A, and influenza B (more than 98.0%), while its positive agreement varied significantly for the abovementioned viral species from 50.0% to 100%. These results highlight the potential of the ID NOW™ COVID-19 2.0 POCT assay as a reliable and rapid tool for excluding SARS-CoV-2 and influenza A/B infections in symptomatic pediatric patients, although its variable positive agreement suggests a need for confirmatory RT-qPCR testing in certain clinical and epidemiological settings in order to ensure accurate diagnosis and appropriate patient management.

Lupus Nephritis from Pathogenesis to New Therapies: An Update.

Lupus Nephritis (LN) still represents one of the most severe complications of Systemic Lupus Erythematosus (SLE) and a major risk factor for morbidity and mortality. However, over the last few years, several studies have paved the way for a deeper understanding of its pathogenetic mechanisms and more targeted treatments. This review aims to provide a comprehensive update on progress on several key aspects in this setting: pathogenetic mechanisms of LN, including new insight into the role of autoantibodies, complement, vitamin D deficiency, and interaction between infiltrating immune cells and kidney resident ones; the evolving role of renal biopsy and biomarkers, which may integrate information from renal histology; newly approved drugs such as voclosporin (VOC) and belimumab (BEL), allowing a more articulate strategy for induction therapy, and other promising phase III-immunosuppressive (IS) agents in the pipeline. Several adjunctive treatments aimed at reducing cardiovascular risk and progression of chronic renal damage, such as antiproteinuric agents, represent an important complement to IS therapy. Furthermore, non-pharmacological measures concerning general lifestyle and diet should also be adopted when managing LN. Integrating these therapeutic areas requires an effort towards a holistic and multidisciplinary approach. At the same time, the availability of an increasingly wider armamentarium may translate into improvements in patient's renal outcomes over the next decades.

Evaluation of Bacterial Viability for Fecal Microbiota Transplantation: Impact of Thawing Temperature and Storage Time.

Fecal Microbiota Transplantation (FMT) represents a promising therapeutic tool under study for several purposes and is currently applied to the treatment of recurrent Clostridioides difficile infection. However, since the use of fresh stool was affected by several issues linked to donor screening, the development of a frozen stool bank is a reliable option to standardize FMT procedures. Nevertheless, different environmental factors impact microbial viability. Herein, we report the effect of different thawing temperatures and storage conditions on bacterial suspensions in the FMT procedure. In total, 20 stool samples were divided into aliquots and tested across a combination of different storing periods (15, 30; 90 days) and thawing procedures (4 °C overnight, room temperature for 1 h; 37 °C for 5 min). Focusing on storage time, our data showed a significant reduction in viability for aerobic and anaerobic bacteria after thawing for 15 days, while no further reductions were observed until after 90 days. Instead, among the different thawing procedures, no significant differences were observed for aerobic bacteria, while for anaerobes, thawing at 37 °C for 5 min was more effective in preserving the bacterial viability. In conclusion, the frozen fecal microbiota remained viable for at least three months, with an excellent recovery rate in all three thawing conditions.

The clinical trial activation process: a case study of an Italian public hospital.

BACKGROUND/AIMS: In order to make the centers more attractive to trial sponsors, in recent years, some research institutions around the world have pursued projects to reorganize the pathway of trial activation, developing new organizational models to improve the activation process and reduce its times. This study aims at analyzing and reorganizing the start-up phase of trials conducted at the Research and Innovation Department (DAIRI) of the Public Hospital of Alessandria (Italy). METHODS: A project was carried out to reorganize the trial authorization process at DAIRI by involving the three facilities responsible for this pathway: clinical trial center (CTC), ethics committee secretariat (ESC), and administrative coordination (AC). Lean Thinking methodology was used with the A3 report tool, and the analysis was carried out by monitoring specific key performance indicators, derived from variables representing highlights of the trials' activation pathway. The project involved phases of analysis, implementation of identified countermeasures, and monitoring of timelines in eight 4-month periods. The overall mean and median values of studies activation times were calculated as well as the average times for each facility involved in the process. RESULTS: In this study, 298 studies both sponsored by research associations and industry with both observational and interventional study design were monitored. The mean trial activation time was reduced from 218 days before the project to 56 days in the last period monitored. From the first to the last monitoring period, each facility involved achieved at least a halving of the average time required to carry out its activities in the clinical trials' activation pathway (CTC: 55 days vs 23, ECS: 25 days vs 8, AC 29 days vs 10). Average activation time for studies with agreement remains longer than those without agreement (100 days vs. 46). CONCLUSIONS: The reorganization project emphasized the importance of having clinical and administrative staff specifically trained on the trial activation process. This reorganization led to the development of a standard operating procedure and a tool to monitor the time (KPIs of the process) that can also be implemented in other clinical centers.

How primary care research can be improved in clinical practice? An Italian case study.

BACKGROUND: Primary care is considered essential for the sustainability of the Health System. Practice-Based Research Networks (PBRN) play a strategic role in translation of primary care research into practice. Research Capacity Building in primary care requires a improvement and development strategy and well-developed research infrastructures to support physicians. METHODS: We used the system development methodology referring to the Lean Thinking to create and support a research team in primary and pediatric care. In particular a "cascade" deployment model and the X-Matrix, a framework used in management studies to support strategy definition and management process. RESULTS: A research unit in primary and pediatric care has been created, by sharing vision, mission, core values, long-term strategies. The definition of a annual planning led to monitoring actions to guarantee the expected goals. CONCLUSIONS: Lean methodology is useful to adapt to various managerial and operational contexts, including healthcare. In our case it allowed team members to spread the culture of research, its importance and role to improve the health of patients, thank to the organizational support of a hospital IR, the Research and Innovation Department.

Clinical Evaluation and Comparison of Two Microfluidic Antigenic Assays for Detection of SARS-CoV-2 Virus.

Given the ongoing pandemic, there is a need to identify SARS-CoV-2 and differentiate it from other respiratory viral infections in various critical settings. Since its introduction, rapid antigen testing is spreading worldwide, but diagnostic accuracy is extremely variable and often in disagreement with the manufacturer's specifications. Our study compared the clinical performances of two microfluidic rapid antigen tests towards a molecular assay, starting from positive samples. A total of 151 swabs collected at the Microbiology and Virology Laboratory of A.O. "SS Antonio e Biagio e C. Arrigo" (Alessandria, Italy) for the diagnosis of SARS-CoV-2 were simultaneously tested to evaluate accuracy, specificity, and agreement with the RT-qPCR results. Both assays showed an overall agreement of 100% for negative specimens, while positive accuracy comprised between 45.10% and 54.90%. According to the manufacturer's instructions, the greatest correlation between the antigenic and molecular assays was observed for the subset with high viral load (18/19, 94.74%), while it dramatically decreased for other subsets. Moreover, the ability to differentiate between SARS-CoV-2 and Flu provides an added value and could be addressed in an epidemic context. However, an in-house validation should be performed due to differences observed in performance declared by manufacturers and those actually obtained.

Rapid RT-PCR identification of SARS-CoV-2 in screening donors of fecal microbiota transplantation.

Since its first appearance in late 2019 in Wuhan, China, severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2) has had a major impact on healthcare facilities around the world. Although in the past year, mass vaccination and the development of monoclonal antibody treatments have reduced the number of deaths and severe cases, the circulation of SARS-CoV-2 remains high. Over the past two years, diagnostics have played a crucial role in virus containment both in health care facilities and at the community level. For SARS-CoV-2 detection, the commonly used specimen type is the nasopharyngeal swab, although the virus can be identified in other matrices such as feces. Since fecal microbiota transplantation (FMT) assumes significant importance in the treatment of chronic gut infections and that feces may be a potential vehicle for transmission of SARS-CoV-2, in this study we have evaluated the performance of the rapid cartridge-based RT-PCR test STANDARD™ M10 SARS-CoV-2 (SD Biosensor Inc., Suwon, South Korea) using fecal samples. The results obtained indicates that STANDARD™ M10 SARS-CoV-2 can detect SARS-CoV-2 in stool samples even at low concentration. For this reason, STANDARD™ M10 SARS-CoV-2 could be used as reliable methods for the detection of SARS-CoV-2 in fecal samples and for the screening of FMT donors.

A machine learning approach for predicting high risk hospitalized patients with COVID-19 SARS-Cov-2.

BACKGROUND: This study aimed to explore whether explainable Artificial Intelligence methods can be fruitfully used to improve the medical management of patients suffering from complex diseases, and in particular to predict the death risk in hospitalized patients with SARS-Cov-2 based on admission data. METHODS: This work is based on an observational ambispective study that comprised patients older than 18 years with a positive SARS-Cov-2 diagnosis that were admitted to the hospital Azienda Ospedaliera "SS Antonio e Biagio e Cesare Arrigo", Alessandria, Italy from February, 24 2020 to May, 31 2021, and that completed the disease treatment inside this structure. The patients'medical history, demographic, epidemiologic and clinical data were collected from the electronic medical records system and paper based medical records, entered and managed by the Clinical Study Coordinators using the REDCap electronic data capture tool patient chart. The dataset was used to train and to evaluate predictive ML models. RESULTS: We overall trained, analysed and evaluated 19 predictive models (both supervised and unsupervised) on data from 824 patients described by 43 features. We focused our attention on models that provide an explanation that is understandable and directly usable by domain experts, and compared the results against other classical machine learning approaches. Among the former, JRIP showed the best performance in 10-fold cross validation, and the best average performance in a further validation test using a different patient dataset from the beginning of the third COVID-19 wave. Moreover, JRIP showed comparable performances with other approaches that do not provide a clear and/or understandable explanation. CONCLUSIONS: The ML supervised models showed to correctly discern between low-risk and high-risk patients, even when the medical disease context is complex and the list of features is limited to information available at admission time. Furthermore, the models demonstrated to reasonably perform on a dataset from the third COVID-19 wave that was not used in the training phase. Overall, these results are remarkable: (i) from a medical point of view, these models evaluate good predictions despite the possible differences entitled with different care protocols and the possible influence of other viral variants (i.e. delta variant); (ii) from the organizational point of view, they could be used to optimize the management of health-care path at the admission time.

Perinatal presepsin assessment: a new sepsis diagnostic tool?

Perinatal sepsis constitutes a medical emergency and is still one of the major causes of mortality and morbidity. The possibility of an early diagnosis of sepsis is still debated and controversial. In particular, clinical symptoms can be hidden by the association of sepsis with other perinatal diseases and/or by therapeutic strategies performed. In this context, there is evidence that the accuracy of standard of care diagnostic parameters (i.e. blood culture, C-reactive protein, procalcitonin) can be biased by additional confounding factors (gestational age, birth-weight, acute-chronic hypoxia). Therefore, the inclusion in clinical daily practice of new biomarkers of sepsis is of utmost importance. Of a panel of biomarkers, Presepsin (P-SEP) plays an important role in the development and response of the immune system and as an early marker of sepsis both in adult and pediatric patients. Therefore, in the present review we aim to offer an overview of the role of P-SEP in the early detection of perinatal sepsis as a trustworthy marker according to actual statements of official international institutions. Future perspectives regard the possibility of a longitudinal non-invasive biological fluids P-SEP assessment thus limiting the sample stress in high risk newborns.

[The organization and staff of a centralized Clinical Trial Center: the Alessandria model.] / L'organizzazione e il personale di un Clinical Trial Center centralizzato: il modello Alessandria.

The case study refers to the Clinical Trial Center (CTC) of the Public Hospital "SS. Antonio e Biagio and Cesare Arrigo" (AO AL) and the Local Health Authority of Alessandria (ASL AL), to which Clinical Research Coordinators (CRCs) and Clinical Research Nurses (CRNs) belong, unique in the regional panorama and a rarity into a public health organization not recognized as Scientific Institute for Research, Hospitalization and Healthcare (IRCCS).

Intragastric prepyloric enteral nutrition, bolus vs continuous in the adult patient: A systematic review and meta-analysis.

Bolus and continuous nutrition are commonly used enteral nutrition (EN) administration methodologies. Currently, there is insufficient evidence to establish which is the most effective method for reducing gastrointestinal complications in adult patients. The aim of this review is to evaluate the impact of bolus/intermittent EN compared with continuous EN for the following outcomes: diarrhea, constipation, emesis/vomiting, gastric residual volume, aspiration, and glycemic control in adult patients receiving intragastric prepyloric EN in the hospital setting. Bibliographical research was performed on the following databases: PubMed, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. The review included all randomized and nonrandomized controlled trials of patients aged ≥18 years with preserved gastrointestinal function. Meta-analysis was performed by Review Manager V.5.3. Seven studies including 551 patients were included in the meta-analysis. Five of these studies reported that the diarrhea rate was higher in the bolus feeding group (risk ratio [RR] = 2.50; 95% CI, 1.17-5.34; P = 0.02), and another five of these studies indicated that the aspiration rate was higher in the continuous feeding group (RR = 0.55; 95% CI, 0.35-0.87; P = 0.01). There were no significant differences for the other outcomes. In conclusion, intermittent EN appears to reduce the incidence of aspiration in the hospital setting; however, it may increase the risk of diarrhea. For future research, we hypothesize the joint use of continuous nutrition until the patient reaches tolerance and then passing to bolus nutrition, thus reducing the incidence of aspiration and enabling a physiological nutrition intake.

Baseline clinical characteristics and prognostic factors in hospitalized COVID-19 patients aged ≤ 65 years: A retrospective observational study.

BACKGROUND: Individual differences in susceptibility to SARS-CoV-2 infection, symptomatology and clinical manifestation of COVID-19 have thus far been observed but little is known about the prognostic factors of young patients. METHODS: A retrospective observational study was conducted on 171 patients aged ≤ 65 years hospitalized in Alessandria's Hospital from 1st March to 30th April 2020 with laboratory confirmed COVID-19. Epidemiological data, symptoms at onset, clinical manifestations, Charlson Comorbidity Index, laboratory parameters, radiological findings and complications were considered. Patients were divided into two groups on the basis of COVID-19 severity. Multivariable logistic regression analysis was used to establish factors associated with the development of a moderate or severe disease. FINDINGS: A total of 171 patients (89 with mild/moderate disease, 82 with severe/critical disease), of which 61% males and a mean age (± SD) of 53.6 (± 9.7) were included. The multivariable logistic model identified age (50-65 vs 18-49; OR = 3.23 CI95% 1.42-7.37), platelet count (per 100 units of increase OR = 0.61 CI95% 0.42-0.89), c-reactive protein (CPR) (per unit of increase OR = 1.12 CI95% 1.06-1.20) as risk factors for severe or critical disease. The multivariable logistic model showed a good discriminating capacity with a C-index value of 0.76. INTERPRETATION: Patients aged ≥ 50 years with low platelet count and high CRP are more likely to develop severe or critical illness. These findings might contribute to improved clinical management.

Innovation in organizational model of the Health Professions Research Unit in an hospital.

BACKGROUND: The organizational model of the Health Professions Research Unit is unique in Italy. It is a centralized sector within of the Intercompany Department of Integrated Activities Research Innovation, afferent to the Complex Infrastructure Research Training Innovation of the SS Antonio e Biagio e Cesare Arrigo Hospital of Alessandria. It emerges from a need to promote, structure and broaden research in the clinical-healthcare field with the primary aim of improving patient care. Its internal organization is represented by a Coordinator Director (PhD) with a function assignment and three research nurses. AIM: Increase scientific production, promote partnerships with scientific communities, encourage the development of professional healthcare networks. METHODS: The definition of specific result indicators on which to estimate the trend of annual activities. The institution of a company network of Department and Structure and the establishment of collaborations with Institutions and Universities. RESULTS: From 2019 to 2021, 11 departmental and 67 Structure referents have been identified; 13 collaborations with National and 3 International Institutions have been activated (42% Increase), 23 clinical trials have been activated (92% increase), 7 articles on impacted journals have been published (100% increase) and 7 are under publication, 27 grey literature papers have been produced (47% increase)and have participated to 5 sponsored calls (100% increase) CONCLUSIONS: The new organizational model established has achieved the objectives set, proving reproducibility in other national and international realities. NURSING IMPLICATIONS: The model could increase at national and international level the scientific production related to the Healthcare professions with important benefits on the clinical outcomes of patients.

Analysis of survival of patients with metastatic malignant pleural mesothelioma.

AIM: To report the outcomes and prognosis of patients with malignant pleural mesothelioma (MPM) who present with or develop metastases during treatment. METHODS: This is a retrospective observational study of patients diagnosed with MPM over 7 years. Metastases at presentation or during follow-up were recorded. Multivariate Cox regression was used to evaluate the relationship of clinicopathologic variables and overall survival (OS). Logistic regression was used for propensity score matching of patients to assess chemotherapy treatment effect. RESULTS: There were 367 patients included with a median age of 71 years (range, 29-91). A total of 69 patients (18%) had metastases: 14 at presentation and 55 during follow-up. Patients presenting with metastases had significantly worse median and 2-year OS compared to those developing metastases during follow-up: 13.3 months (95% confidence interval [CI], 2-24.6 months) and 0% versus 20.2 months (95% CI, 16.7-23.3 months) and 33%, respectively (p = 0.029). Female sex, age >70 years, nonepithelioid histology, and not receiving chemotherapy were independent poor prognostic factors. There was no difference in OS of patients with locally advanced (T4) disease compared to metastatic disease (M1): median OS 10.7 months (95% CI, 5.9-15.6) versus 13.3 months (95% CI, 2-24.6) (p = 0.18), respectively. Following propensity matching, sarcomatoid histology (hazard ratio, 7.86 [95% CI, 3.64-16.95]; p < 0.001) and multiple lines of chemotherapy (hazard ratio, 0.38 [95% CI, 0.19-0.84]; p = 0.015) were significant independent prognostic factors for OS. CONCLUSIONS: T4 disease carries a similar OS as metastatic MPM. Female sex, advanced age, nonepithelioid histology, and not receiving chemotherapy were independent poor prognostic factors.

SARS-CoV-2 infection as a trigger of autoimmune response.

Currently, few evidences have shown the possible involvement of autoimmunity in patients affected by coronavirus disease 2019 (COVID-19). In this study, we elucidate whether severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) stimulates autoantibody production and contributes to autoimmunity activation. We enrolled 40 adult patients (66.8 years mean age) admitted to Alessandria Hospital between March and April 2020. All the patients had a confirmed COVID-19 diagnosis and no previously clinical record of autoimmune disease. Forty blood donors were analyzed for the same markers and considered as healthy controls. Our patients had high levels of common inflammatory markers, such as C reactive protein, lactate dehydrogenase, ferritin, and creatinine. Interleukin-6 concentrations were also increased, supporting the major role of this interleukin during COVID-19 infection. Lymphocyte numbers were generally lower compared with healthy individuals. All the patients were also screened for the most common autoantibodies. We found a significant prevalence of antinuclear antibodies, antineutrophil cytoplasmic antibodies, and ASCA immunoglobulin A antibodies. We observed that patients having a de novo autoimmune response had the worst acute viral disease prognosis and outcome. Our results sustain the hypothesis that COVID-19 infection correlates with the autoimmunity markers. Our study might help clinicians to: (a) better understand the heterogeneity of this pathology and (b) correctly evaluate COVID-19 clinical manifestations. Our data explained why drugs used to treat autoimmune diseases may also be useful for SARS-CoV-2 infection. In addition, we highly recommend checking patients with COVID-19 for autoimmunity markers, mainly when deciding on whether to treat them with plasma transfer therapy. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? ☑ Recent data sustain the idea that autoimmune phenomena exist in patients with coronavirus disease 2019 (COVID-19), but other investigations are necessary to define the possible link between severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection and autoimmune disease onset. WHAT QUESTION DID THIS STUDY ADDRESS? ☑ In this monocentric study, we demonstrated how SARS-CoV-2 infection could be associated with an autoimmune response and development of autoantibodies. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? ☑ Patients with COVID-19 having an increased level of inflammatory markers and strong autoantibodies positivity (i.e., antinuclear antibodies and antineutrophil cytoplasmic antibodies) presented the worst clinical outcome. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? ☑ These results suggest that the drugs normally used to treat autoimmune diseases should also be considered during SARS-CoV-2, improving public health. In addition, before starting a transfer plasma therapy, it is important to also evaluate the autoimmunity conditions of the patients with COVID-19. Transferring antibodies or trying to neutralize them should be done with precaution. It is possible that the risk of developing or increasing the autoimmune response may enhance.

Physiopathology of the diabetic bladder.

OBJECTIVE: To investigate the incidence of diabetic cystopathy in relation to age, gender, type of diabetes, duration of diabetic disease and clinical evidence of peripheral neuropathy and to analyze the physiopathology of the various forms of diabetic cystopathy due to sensory impairment, motor-sensory impairment, motor impairment and hyperreflexia. MATERIALS AND METHODS: In a retrospective multicenter cohort study the medical records of a cohort of 126 diabetic patients with (128 patients) or without (48 patients) urological symptoms were analyzed. Patients were observed at the Città di Alessandria Clinic of Policlinico di Monza and/or at the outpatient clinic of Alessandria Hospital from June 2018 to June 2020. The study excluded patients with central and/or peripheral neuropathy, spina bifida (mylomeningocele or meningocele) or spina bifida occulta; with persistent urinary infections; in anticholinergic treatment for enteric dysfunctions; in medical treatment for cervical-prostatic-urethral obstruction; with vaginal and/or rectal prolapse of II, III, IV degree; with previous spinal or pelvic surgery including radical prostatectomy, Wertheim hysterectomy or colorectal surgery. All the patients were studied with computed tomography (CT) scan of the urinary tract, voiding cystourethrography (VCUG), uroflowmetry, cystomanometry with intrinsic pressure assessment and compliance evaluation, electromyography (EMG) of the anal sphincter, pressure flow analysis, urethral pressure profile and, when advised, pharmacological tests. RESULTS: Out of 126 diabetic patients, 48 did not show any signs or symptoms of urine voiding dysfunction; 30 were men and 18 women with an average age of 62.6 years; 20 had type I diabetes and were in treatment with insulin and 28 type II diabetes treated with oral hypoglycemic medication. The remaining 78 patients (48 men and 30 women), with an average age of 64.8 years, presented urological symptoms; 31 had type I diabetes and 47 had II type diabetes. CONCLUSIONS: Diagnosis of the various forms of diabetic cystopathy and early treatment decreases complications and consequently accesses to outpatient facilities and hospital admissions, resulting in an improved quality of life.

Decrease and Delay in Hospitalization for Acute Coronary Syndromes During the 2020 SARS-CoV-2 Pandemic.

The diffusion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) forced the Italian population to restrictive measures that modified patients' responses to non-SARS-CoV-2 medical conditions. We evaluated all patients with acute coronary syndromes admitted in 3 high-volume hospitals during the first month of SARS-CoV-2 Italian-outbreak and compared them with patients with ACS admitted during the same period 1 year before. Hospitalization for ACS decreased from 162 patients in 2019 to 84 patients in 2020. In 2020, both door-to-balloon and symptoms-to-percutaneous coronary intervention were longer, and admission levels of high-sensitive cardiac troponin I were higher. They had a lower discharged residual left-ventricular function and an increased predicted late cardiovascular mortality based on their Global Registry of Acute Coronary Events (GRACE) scores.

Totally robotic soave pull-through procedure for Hirschsprung's disease: lessons learned from 11 consecutive pediatric patients.

INTRODUCTION: Since Hirschsprung's disease (HSCR) already proved to benefit from robotic surgery, we aimed at describing a wider series of patients with this rare disease who were operated on with a robotic approach. PATIENTS AND METHODS: All consecutive HSCR patients who underwent totally robotic soave pull-through (TRSPT), between October 2015 and June 2019, have been included. Ethical Committee approval was obtained. Data regarding clinical features, technical details, complications, hospital stay, and functional outcome have been prospectively collected for each patient. RESULTS: Eleven patients have been included. Mean age at surgery was 29 months. Median length of surgery was 420 min. Median console time was 180 min. Six patients suffered from rectosigmoid aganglionosis, three from long HSCR (extending up to the hepatic flexure), two from total colonic aganglionosis. No major intraoperative complications occurred. Four patients (three of whom carrying a stoma) experienced minor mucosal tearing during dissection. One anastomotic stricture required dilatation under general anesthesia and two cuff strictures required cuff release (both occurring in patients who experienced intraoperative mucosal tearing). Follow-up lasted a median of 12 months. One patient experienced mild postoperative enterocolitis. Continence scored excellent-to-good in all patients who could be assessed on that regard (7 out of 11). CONCLUSIONS: Provided a number of technical key points are respected, the outcome of TRSPT for HSCR is promising. Younger patients, particularly those carrying a stoma, proved to be technically demanding and deserve a longer learning curve. Accurate preoperative bowel preparation, correct trocar placement and patient positioning proved to be crucial aspects of treatment. To conclude, TRSPT is particularly suitable for older HSCR patients, even those requiring a redo, and represents a valid alternative to available surgical option for this delicate subgroup of HSCR patients.

Management of recurrent pleural mesothelioma: Successful rechallenge with nintedanib in combination with chemotherapy.

Malignant pleural mesothelioma (MPM) is a rare neoplasm, generally caused by asbestos exposure. This case details how a patient treated with nintedanib during the LUME-Meso study was rechallenged with nintedanib. The findings highlight the benefit of nintedanib rechallenge and the potential use of continuous anti-angiogenic therapy in MPM treatment.