Exceptionally rich keratinolytic enzyme profile found in the rare actinomycetes Amycolatopsis keratiniphila D2T.

The non-spore forming Gram-positive actinomycetes Amycolatopsis keratiniphila subsp. keratiniphila D2T (DSM 44,409) has a high potential for keratin valorization as demonstrated by a novel biotechnological microbial conversion process consisting of a bacterial growth phase and a keratinolytic phase, respectively. Compared to the most gifted keratinolytic Bacillus species, a very large number of 621 putative proteases are encoded by the genome of Amycolatopsis keratiniphila subsp. keratiniphila D2T, as predicted by using Peptide Pattern Recognition (PPR) analysis. Proteome analysis by using LC-MS/MS on aliquots of the supernatant of A. keratiniphila subsp. keratiniphila D2T culture on slaughterhouse pig bristle meal, removed at 24, 48, 96 and 120 h of growth, identified 43 proteases. This was supplemented by proteome analysis of specific fractions after enrichment of the supernatant by anion exchange chromatography leading to identification of 50 proteases. Overall 57 different proteases were identified corresponding to 30% of the 186 proteins identified from the culture supernatant and distributed as 17 metalloproteases from 11 families, including an M36 protease, 38 serine proteases from 4 families, and 13 proteolytic enzymes from other families. Notably, M36 keratinolytic proteases are prominent in fungi, but seem not to have been discovered in bacteria previously. Two S01 family peptidases, named T- and C-like proteases, prominent in the culture supernatant, were purified and shown to possess a high azo-keratin/azo-casein hydrolytic activity ratio. The C-like protease revealed excellent thermostability, giving promise for successful applications in biorefinery processes. Notably, the bacterium seems not to secrete enzymes for cleavage of disulfides in the keratinous substrates. KEY POINTS: • A. keratiniphila subsp. keratiniphila D2T is predicted to encode 621 proteases. • This actinomycete efficiently converts bristle meal to a protein hydrolysate. • Proteome analysis identified 57 proteases in its secretome.

Efficacy of tocilizumab in patients with COVID-19 ARDS undergoing noninvasive ventilation.

BACKGROUND: The severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is extremely variable, ranging from asymptomatic patients to those who develop severe acute respiratory distress syndrome (ARDS). As for now, there are still no really effective therapies for coronavirus disease 2019 (COVID-19). Some evidences suggest that tocilizumab (TCZ) may avoid the progression of severe COVID-19. The aim of this retrospective case-control study was to analyze the efficacy and safety of TCZ in patients with COVID-19 ARDS undergoing noninvasive mechanical ventilation (NIV). METHODS: Seventy-nine consecutive patients with severe COVID-19 pneumonia and worsening acute respiratory failure (ARF) were admitted to the Pulmonology Unit of Azienda USL of Reggio Emilia-IRCCS. All patients were inflamed (elevated CRP and IL-6 levels) and received NIV at admission according to the presence of a pO2/FiO2 ratio ≤ 200 mmHg. The possibility of being treated with TCZ depended on the drug availability. The primary outcome was the in-hospital mortality rate. A secondary composite outcome of worsening was represented by the patients who died in the pulmonology unit or were intubated. RESULTS: Out of 79 patients, 41 were treated with TCZ. Twenty-eight patients received intravenous (IV) TCZ and 13 patients received subcutaneous (SC) TCZ. In-hospital overall mortality rate was 38% (30/79 patients). The probabilities of dying and being intubated during the follow-up using Kaplan-Meier method were significantly lower in total patients treated with TCZ compared to those of patients not treated with TCZ (log-rank p value = 0.006 and 0.036, respectively). However, using Cox multivariate analyses adjusted for age and Charlson comorbidity index only the association with the reduced risk of being intubated or dying maintained the significance (HR 0.44, 95%CI 0.22-0.89, p = 0.022). Two patients treated with TCZ developed cavitating lung lesions during the follow-up. CONCLUSIONS: This study shows that TCZ treatment may be effective in COVID-19 patients with severe respiratory impairment receiving NIV. More data on safety are required. Randomized controlled trials are needed to confirm these results.

Two novel S1 peptidases from Amycolatopsis keratinophila subsp. keratinophila D2T degrading keratinous slaughterhouse by-products.

Two proteases, named C- and T-like proteases, respectively, were purified from the culture supernatant of Amycolatopsis keratinophila subsp. keratinophila D2T grown on a keratinous slaughterhouse by-product of pig bristles and nails as sole nitrogen and carbon source. The two proteases belong to peptidase family S1 as identified by mass spectrometric peptide mapping, have low mutual sequence identity (25.8%) and differ in substrate specificity. T-like protease showed maximum activity at 40 °C and pH 8-9, and C-like protease at 60 °C and pH 8-10. Peptides released from the keratinous by-product were identified by mass spectrometry and indicated P1 specificity for arginine and lysine of T-like and alanine, valine and isoleucine of C-like protease as also supported by the activity of the two proteases towards synthetic peptide and amino acid substrates. The specific activities of the C- and T-like proteases and proteinase K on keratin azure and azokeratin were comparable. However, C- and T-like proteases showed 5-10-fold higher keratin/casein (K/C) activity ratios than that of another S1 and two keratin-degrading S8 peptidases used for comparison. The findings support that the range of peptidase families considered to contain keratinases should be expanded to include S1 peptidases. Furthermore, the results indicated the quite thermostable C-like protease to be a promising candidate for use in industrial degradation of keratinous slaughterhouse by-products.

Is early integration of palliative care feasible and acceptable for advanced respiratory and gastrointestinal cancer patients? A phase 2 mixed-methods study.

BACKGROUND: There is evidence that early integration of palliative care improves quality of life, lowers spending and helps clarify preferences and goals for advanced cancer patients. Little is known about the feasibility and acceptability of early integration. AIM: Assessing feasibility of early integration of palliative care, and exploring concerns perceived and problems encountered by patients, relatives and oncologists. DESIGN: A phase 2 mixed-methods study ( ClinicalTrials.Gov :NCT02078700). METHODS: Oncologists of two outpatient clinics offered a specialised palliative care intervention integrated with standard oncological care to all consecutive newly diagnosed metastatic respiratory/gastrointestinal cancer patients. We interviewed samples of patients, relatives and oncologists to explore strengths and weaknesses of the intervention. RESULTS: The intervention was proposed to 44/54 eligible patients (81.5%), 40 (90.1%) accepted, 38 (95.0%) attended the first palliative care visit. The intervention was completed for 32 patients (80.0%). It did not start for three (7.5%) and was interrupted for three patients who refused (7.5%). The Palliative Care Unit performed 274 visits in 38 patients (median per patient 4.5), and 24 family meetings with relatives of 16 patients. All patients and most relatives referred to the usefulness of the intervention, specifically for symptoms management, information and support to strategies for coping. Oncologists highlighted their difficulties in informing patients on palliative intervention, sharing information and coordinating patient's care with the palliative care team. CONCLUSION: Early integration of palliative care in oncological setting seems feasible and well accepted by patients, relatives and, to a lesser extent, oncologists. Some difficulties emerged concerning patient information and inter-professional communication.

Psychological health in long-term cancer survivorship: an Italian survey on depression and anxiety.

Since long-term survivorship is now a reality for an increasingly number of people with a history of cancer, understanding their psychological health can inform health care policy as well as help supporting individual patients. This study was aimed to describe depression and anxiety (i.e. two of the most common psychological symptoms reported in oncology) in a sample of Italian long-term cancer survivors (LTCSs) defined as people who have been free from cancer and cancer treatments for at least five years. Four hundred and four Italian adult LTCSs completed a battery of questionnaires including the Zung Self-rating Depression Scale and the State Anxiety sub-scale of the State-Trait Anxiety Inventory respectively for depression and anxiety assessment. 16.5% of the sample displayed mild depression, 11.1% moderate depression, and 7.1% severe depression. depression was negatively associated with education (p = .017), perceived social support as provided by the family (p = .028), and perceived social support provided by friends (p = .008), and it was positively associated with occupational status (p = .023), presence of health issues (p = .010), and anxiety (p < .001). 8.7 and 15.8% of the sample were respectively possible and probable cases of anxiety. Anxiety was negatively associated with occupational status (p = .038) and it was positively associated with depression (p < .001). These data support ongoing assessment and monitoring of depression and anxiety in LTCSs, and stimulate the development and testing of psychological interventions for such individuals. In addition, they encourage further study on the psychological health of this specific population.

Is long-term cancer survivors' quality of life comparable to that of the general population? An italian study.

PURPOSE: Since long-term survivorship is now a reality for an increasingly number of people with a history of cancer, understanding their quality of life (QoL) can inform health care policy as well as help supporting individual patients. This study was aimed to quantify QoL of this specific population in comparison with data provided for both the general population and cancer patients and to assess QoL association with several sociodemographic, clinical, and psychological variables. METHODS: Three hundred fourteen Italian long-term cancer survivors (people who have been free from cancer and cancer treatments for at least 5 years) completed a battery of questionnaires including the SF12 for QoL assessment. RESULTS: Both physical and mental functioning were higher than those among Italian cancer patients but lower than those of the Italian general population (p < .001). Poorer QoL (physical and mental functioning) was associated more often with psychological conditions (as anxiety and depression) than with sociodemographic and cancer-related variables. CONCLUSIONS: These data support an ongoing specific interest in the QoL of long-term cancer survivors and suggest the need for further study of multidimensional functioning in this population.

Effectiveness of noninvasive ventilation in COVID-19 related-acute respiratory distress syndrome.

INTRODUCTION: During this long COVID-19 pandemic outbreak, continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) are being widely used to treat patients with moderate to severe acute respiratory failure (ARF). As for now, data on the efficacy of NIV in COVID-19 acute respiratory distress syndrome (ARDS) are lacking, and for this reason it is extremely important to accurately determine the outcomes of this strategy. This study aimed to evaluate clinical data and outcomes of NIV in patients with COVID-19 ARDS. MATHERIALS AND METHODS: Seventy-nine consecutive patients with sudden worsening of respiratory failure were evaluated. All patients (71% male) had a confirmed SARS-CoV-2 infection and signs, symptoms and radiological findings compatible with COVID-19 pneumonia and all of them underwent a trial of NIV. Primary outcomes were NIV success and failure defined by intubation and mortality rate. Secondary outcome was the duration of NIV. RESULTS: NIV was successful in 38 (48.1%) patients (Table 1). EOT was necessary in 21 patients (26.6%). Death occurred in 20 patients (25.3%). In the group of patients having failed a trial with NIV and then being intubated, compared to those who continued NIV, there was no higher mortality rate. By evaluating the ICU survival outcome of the subgroup of patients intubated after NIV, 57% of the patients were discharged and 43% died. CONCLUSION: Previous studies conducted on patients undergoing invasive mechanical ventilation showed higher mortality rate than the present study. Our data showed that NIV can avoid intubation in almost half of the patients. Therefore, this data could reassure clinicians who would consider using NIV in COVID-19 ARDS-related treatment.

Azo dying of α-keratin material improves microbial keratinase screening and standardization.

Microbial conversion through enzymatic reactions has received a lot of attention as a cost-effective and environmentally friendly way to recover amino acids and short peptides from keratin materials. However, accurate assessment of microbial keratinase activity is not straightforward, and current available methods lack sensitivity and standardization. Here, we suggest an optimized Azokeratin assay, with substrate generated directly from azo-dyed raw keratin material. We introduced supernatant filtration in the protocol for optimal stopping of keratinase reactions instead of the widely used trichloroacetic acid (TCA), as it generated biases and impacted the sensitivity. We furthermore suggest a method for standardization of keratinase activity signals using proteinase K, a well-known keratinase, as a reference enabling reproducibility between studies. Lastly, we evaluated our developed method with several bacterial isolates through benchmarking against a commercial assay (Keratin Azure). Under different setups, the Azokeratin method was more sensitive than commonly used Keratin Azure-based assays (3-fold). We argue that this method could be applied with any type of keratin substrate, enabling more robust and sensitive results which can be used for further comparison with other studies, thus representing an important progress within the field of microbial keratin degradation.

Integrated intErventional bronchoscopy in the treatment of locally adVanced non-small lung cancER with central Malignant airway Obstructions: a multicentric REtrospective study (EVERMORE).

OBJECTIVES: Despite new therapeutic perspectives, the presence of central airways occlusion (CAO) in patients with locally advanced non-small cell lung cancer (NSCLC) is associated with poor survival. There is no clear evidence on the clinical impact of interventional bronchoscopy as a part of an integrated treatment to cure these patients. MATERIALS AND METHODS: This retrospective cohort study was conducted in two teaching hospitals over a 10 years period (January 2010-January 2020) comparing patients with NSCLC at stage IIIB and CAO at disease onset treated with chemotherapy/radiotherapy (standard therapy-ST) with those receiving interventional bronchoscopy plus ST (integrated treatment-IT). Primary outcome was 1-year survival. The onset of respiratory events, symptoms-free interval, hospitalization, need for palliation, and overall mortality served as secondary outcomes. RESULTS: A total of 100 patients were included, 60 in the IT and 40 in the ST group. Unadjusted Kaplan-Meier estimates showed greater effect of IT compared to ST on 1-year survival (HR = 2.1 95%CI[1.1-4.8], p = 0.003). IT showed a significantly higher survival gain over ST in those patients showing KRAS mutation (7.6 VS 0.8 months,<0.0001), a lumen occlusion >65% (6.6 VS 2.9 months,<0.001), and lacking the involvement of left bronchus (7 VS 2.3 months,<0.0001). Compared to ST, IT also showed a favorable difference in terms of new hospitalizations (p = 0.03), symptom-free interval (p = 0.02), and onset of atelectasis (p = 0.01). CONCLUSIONS: In patients with NSCLC stage IIIB and CAO, additional interventional bronchoscopy might impact on 1-year survival. Genetic and anatomic phenotyping might allow identifying those patients who may gain life expectancy from the endoscopic intervention.

An integrated strategy for the effective production of bristle protein hydrolysate by the keratinolytic filamentous bacterium Amycolatopsis keratiniphila D2.

In a conventional microorganism-mediated biological process for degradation of keratinous waste material the production of keratin-specific proteases (i.e., keratinases) and the hydrolysis of keratin-rich residual biomass both take place during the same stage of the bioprocess and, as a consequence, occur simultaneously under suboptimal conditions. In the present study the keratinolytic actinomycete Amycolatopsis keratiniphila D2 was successfully employed to biodegrade thermally pretreated porcine bristles at high solids loading (16% w/v) via a novel cultivation methodology. Indeed, the two-stage submerged fermentation process developed in this work enabled to efficiently recover, in a single unit operation, about 73% of the protein material contained in the keratinous biowaste structure, resulting in an overall accumulation of 89.3 g·L-1 protein-rich hydrolysate and a productivity of 427 mg crude soluble proteins per litre per hour. The obtained protein hydrolysate powder displayed a 2.2-fold increase in its in vitro pepsin digestibility (95%) with respect to the non-hydrolysed pretreated substrate (43%). In addition, the chromatogram obtained by size-exclusion chromatography analysis of the final product indicated that, among the identified fractions, those consisting of small peptides and free amino acids were the most abundantly present inside the analysed sample. Given these facts it is possible to conclude that the soluble proteins, peptides and free amino acids recovered through the newly designed two-stage bioextraction process could represent a viable alternative source of protein in animal feed formulation.

Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

This review summarizes the main pathophysiological basis of the relationship between metabolic syndrome, endocrine disruptor exposure and prostate cancer that is the most common cancer among men in industrialized countries. Metabolic syndrome is a cluster of metabolic and hormonal factors having a central role in the initiation and recurrence of many western chronic diseases including hormonal-related cancers and it is considered as the world's leading health problem in the coming years. Many biological factors correlate metabolic syndrome to prostate cancer and this review is aimed to focus, principally, on growth factors, cytokines, adipokines, central obesity, endocrine abnormalities and exposure to specific endocrine disruptors, a cluster of chemicals, to which we are daily exposed, with a hormone-like structure influencing oncogenes, tumor suppressors and proteins with a key role in metabolism, cell survival and chemo-resistance of prostate cancer cells. Finally, this review will analyze, from a molecular point of view, how specific foods could reduce the relative risk of incidence and recurrence of prostate cancer or inhibit the biological effects of endocrine disruptors on prostate cancer cells. On the basis of these considerations, prostate cancer remains a great health problem in terms of incidence and prevalence and interventional studies based on the treatment of metabolic syndrome in cancer patients, minimizing exposure to endocrine disruptors, could be a key point in the overall management of this disease.

Correction: Metabolic syndrome, endocrine disruptors and prostate cancer associations: biochemical and pathophysiological evidences.

[This corrects the article DOI: 10.18632/oncotarget.16725.].

A 7-Year Retrospective Multisource Analysis on the Incidence of Anesthesia Awareness With Recall in Cancer Patients: A Chance of Collaboration Between Anesthesiologists and Psycho-Oncologists for Awareness Detection.

Although randomized controlled studies reported an incidence of anesthesia awareness with recall ∼1 to 2 per 1000 (0.1-0.2%), recent data from the NAP5 study showed an incidence of only 1:19,600. Although in a prospective study many tools for anesthesia awareness detection can be used, a retrospective analysis requires a careful collection of information.The aim of the study was to evaluate the incidence of anesthesia awareness with recall in a cohort of cancer patients through a multisource retrospective analysis, and the clinical description, including the psychological outcome, of the cases detected. We also tested whether our retrospective analysis would be improved by a routinely psycho-oncological assessment. As secondary endpoints we evaluated the use of depth of anesthesia monitoring over a large cohort of patients, and the correlation between the brain monitoring and the incidence of awareness.We have carried out a 7-year retrospective analysis in a large cohort of cancer patients on the incidence of awareness with recall during general anesthesia. Of 35,595 patients assessed for eligibility, 21,099 were studied. We analyzed all data from the operative rooms' database, the anesthesia records, and from the database of the surgical divisions. In addition we examined reports from psychologists and spontaneous reports to the quality team of the hospital.Two certain cases of awareness were detected, with an incidence of 1:10,550 (0.0095%). They occurred during elective surgery, in female patients without other risk factors. One case came from the report of a psychologist. In both episodes, brain monitoring was not applied and no long-term psychological sequelae were reported.Despite the limitations, our investigation suggests that the incidence of anesthesia awareness is very low, also in a specific cohort of patients, such as the cancer patients, and even when the depth of anesthesia monitoring is rarely used. The limitations caused by both the retrospective analysis and the absence of specific tools for direct awareness detection, such as structured interviews, can be filled with an effective postoperative psychological assessment which is often of routine in a cancer center. This observation could suggest the usefulness of inserting specific questions within the psychological tools commonly used by psycho-oncologists.

Role of DNA repair machinery and p53 in the testicular germ cell cancer: a review.

Notwithstanding the peculiar sensitivity to cisplatin-based treatment, resulting in a very high percentage of cures even in advanced stages of the disease, still we do not know the biological mechanisms that make Testicular Germ Cell Tumor (TGCT) "unique" in the oncology scene. p53 and MDM2 seem to play a pivotal role, according to several in vitro observations, but no correlation has been found between their mutational or expression status in tissue samples and patients clinical outcome. Furthermore, other players seem to be on stage: DNA Damage Repair Machinery (DDR) , especially Homologous Recombination (HR) proteins, above all Ataxia Telangiectasia Mutated (ATM), cooperates with p53 in response to DNA damage, activating apoptotic cascade and contributing to cell "fate". Homologous Recombination deficiency has been assumed to be a Germ Cell Tumor characteristic underlying platinum-sensitivity, whereby Poly(ADP-ribose) polymerase (PARP), an enzyme involved in HR DNA repair, is an intriguing target: PARP inhibitors have already entered in clinical practice of other malignancies and trials are recruiting TGCT patients in order to validate their role in this disease. This paper aims to summarize evidence, trying to outline an overview of DDR implications not only in TGCT curability, but also in resistance to chemotherapy.

Pulmonary involvement in an adult female affected by type B Niemann Pick disease.

We describe the case of a 33-year-old woman who presented with a pattern of diffuse micronodular opacities with centrolobular distribution at high resolution chest tomography (HRCT) performed after exposure to the smoke of a home fire. An abdominal CT scan showed the presence of 3 rounded hypodense lesions in the spleen parenchyma. A bronchoalveolar lavage (BAL) was performed, showing the presence of lipid laden cells in the aspirated fluid. A video-assisted thoracoscopic biopsy confirmed the presence of the foamy cells filling the alveolar spaces and showed a preserved background pulmonary architecture; the bronchiolar epithelium presented a cytoplasm with a particularly clear colour. Foam cells were present in the bone marrow aspirate too, that contained also sea-blue histiocytes. These data induced us to consider the diagnosis of a metabolic storage disorder, in the first instance Niemann-Pick type B, that was confirmed by low acid lysosomal sphingomyelinase activity on cultured fibroblasts: 5.22 nmol/mg prot/h (n.v. 92 +/- 18.2). Lung involvement is an important complication of Niemann-Pick disease, presenting with the clinical and radiological features of a diffuse lung disease.

Solitary choroidal metastasis from atypical carcinoid of the lung detected by (68)Ga DOTATATE PET/CT.

A 71-year-old woman with a history of surgically treated bronchial atypical carcinoid underwent Ga DOTATATE PET/CT for restaging. Somatostatin receptor PET/CT revealed a focal area of mild radiopharmaceutical uptake corresponding to a thickening of the right choroid. No other areas of abnormal tracer uptake were detected in the rest of the body. Based on these PET/CT findings, the patient underwent examination of fundus oculi, MRI, and fluoroangiography, which confirmed the presence of a choroidal lesion interpreted as solitary choroidal metastasis of neuroendocrine tumor. Subsequently, the patient was referred for brachytherapy with radical intent.

Well-differentiated giant "lipoma-like" liposarcoma of the posterior mediastinum: a case report.

While liposarcoma is the most common malignant mesenchymal neoplasm in adults, a mediastinal position is rare. We describe here the case of a 74-year-old female with an hourglass-shaped mass in the posterior mediastinum, which was probably present on a roentgenogram 4 years earlier. On a CT scan of the chest, the mass appeared non-homogeneous with a mainly adipose content. A preoperative ultrasonically guided tru-cut transthoracic biopsy revealed the presence of adipose tissue with mildly atypical cytological features. The mass was therefore completely excised by means of a right thoracotomy. The postoperative course was uneventful and the patient is alive and well and has had no recurrence in the 6 months since surgery. We review here the natural history, pathology, and prognosis of the disease, and discuss methods of diagnosis and management of such lesions.

Strengths and weaknesses in the determination of Saccharomyces cerevisiae cell viability by ATP-based bioluminescence assay.

Due to its sensitivity and speed of execution, detection of ATP by luciferin-luciferase reaction is a widely spread system to highlight cell viability. The paper describes the methodology followed to successfully run the assay in the presence of yeast cells of two strains of the yeast Saccharomyces cerevisiae, BY4741 and CEN.PK2-1C and emphasizes the importance of correctly determining the contact time between the lysing agent and the yeast cells. Once this was established, luciferin-luciferase reaction was exploited to determine the maximum specific rate of growth, as well as cell viability in a series of routine tests. The results obtained in this preliminary study highlighted that using luciferin-luciferase can imply an over-estimation of maximum specific growth rate with respect to that determined by optical density and/or viable count. On the contrary, the bioluminescence assay gave the possibility to highlight, if employed together with viable count, physiological changes occurring in yeast cells as response to stressful environmental conditions such as those deriving from exposure of yeast cells to high temperature or those depending on the operative conditions applied during fed-batch operations.

Prospective, multicenter, randomized trial of a new organizational modality for providing information and support to cancer patients.

PURPOSE: No structured modality for providing information and support to patients in oncology wards has been validated in clinical trials. METHODS: This is a pragmatic, two-arm, cluster randomized trial, with the oncology ward as random assignment unit. Centers were allocated to implement a Point of Information and Support (PIS) or to a control group. The PIS included a library for cancer patients and a specifically trained oncology nurse. End points, measured at patient level, were psychological distress and satisfaction with received information. Both intent-to-treat and per-protocol analyses considering clustering were performed. RESULTS: Thirty-eight Italian cancer centers were randomly assigned, and 6 months after PIS creation, 3,286 unselected, consecutive cancer patients were surveyed (1,654 in the experimental group and 1,632 in the control group). Three thousand one hundred ninety-seven (97%) questionnaires were collected and deemed valid. Fifty-two percent of centers (11 of 21 centers) in the experimental arm did not implement the PIS in accordance with the protocol. Overall, 34% of patients showed moderate to severe psychological distress, and only 9% declared dissatisfaction. Intent-to-treat analysis did not yield significant differences. Although the per-protocol analysis did show a reduction in psychological distress (28.9% for functioning PIS v 33.3% for no PIS) and dissatisfaction (6.4% for functioning PIS v 9.3% for no PIS), differences did not reach significance. CONCLUSION: This is the first cluster randomized trial aiming to demonstrate that a structured modality of providing information reduces psychological distress. We did not find this, but we believe results should be interpreted cautiously, particularly because of the low compliance with PIS implementation. Context analysis preceding such interventions is essential.