The Path of Cicely Saunders: The "Peculiar Beauty" of Palliative Care.

This paper is aimed at focusing on the writings and the experience of the Hospice movement Founder, Dame Cicely Saunders. The in-depth analysis carried out had the objective of verifying if "the way" of Cicely to understand, live and propose palliative care was still current and "beautiful", so that we can nowadays refer to her fascinating "Original Palliative Care". With "beauty" we mean, on the one hand, a way able to allow a personal path of research of the meaning of the disease and of the care, both for those who care and for those who are cared for. On the other hand, it seems to us that Cicely strongly suggests how this path can not be carried out alone, but is only possible within the context of a network of relationships and support, in a so called "relational autonomy", for the patient, included in a "care ethics". The authors believe that the work extensively documents as the overall approach of Cicely, traditional but always to be rediscovered, is still today the most convincing way of conception and action of palliative care.

Early palliative care and quality of life of advanced cancer patients-a multicenter randomized clinical trial.

BACKGROUND: To compare quality of life (QoL) of patients receiving early palliative care (EPC) vs. standard oncologic care (SOC). METHODS: Pragmatic, multicenter, randomized trial at five University and Community Hospital Cancer Centers in Northern Italy. Advanced non-small cell lung, gastric, pancreatic and biliary tract cancer patients diagnosed within the previous 8 weeks. In the EPC arm, visits were performed systematically by a dedicated physician/nurse palliative care (PC) team, who assessed physical and psychosocial symptoms, and enacted the necessary services. In the SOC arm, PC visits were only carried out if requested. The primary outcome was the difference in the change of QoL [Functional Assessment of Cancer Therapy-General measure (FACT-G)] from baseline to 12 weeks in the two groups. RESULTS: From November 2014 to March 2016, 281 patients were enrolled (142 EPC, 139 SOC); 218 completed FACT-G at 12 weeks. Baseline demographic and clinical characteristics were similar for the two groups. Values of FACT-G at baseline and 12 weeks were 72.3 (SD 12.6) and 70.1 (SD 15.5) for patients enrolled in the EPC arm, vs. 71.7 (SD 14.7) and 69.6 (SD 15.5) for the SOC arm, but the change scores did not differ significantly between groups. In the multivariable analysis, adjusting for QoL at baseline, two potential prospective prognostic factors were statistically significant: lung cancer (P=0.03) and interaction of living without a partner and intervention arm (P=0.01). Dying within 6 months (P<0.001) was also statistically significant. CONCLUSIONS: In this study, EPC did not improve QoL in advanced cancer patients, but our findings highlight aspects which may guide future research on EPC.

Symptom expression in advanced cancer patients admitted to hospice or home care with and without delirium.

The aim of this study is to investigate the relationship between delirium and symptom expression in advanced cancer patients admitted to palliative care services. This is a secondary analysis of a consecutive sample of advanced cancer patients who were admitted to home care and hospices, and prospectively assessed for a period of 10 months. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS (Memorial Delirium Assessment Scale) were measured at admission (T0) and after seven days of home care or hospice care (T7). Of the eight hundred and forty-eight patients screened in the period, 585 were not considered in the analysis for various reasons. The mean age was 72.1 years (SD 13.7), and 146 patients were males (55.5%). The mean Karnofsky status recorded at T0 is 34.1 (SD = 6.69). The mean duration palliative care assistance is 38.4 days (SD = 48, range 2-220). Of 263 patients who had a MDAS available at T0, 110 patients (41.8%) had a diagnosis of delirium. Of them, 167 patients had complete data regarding MDAS measurement, either at T0 and T7. A larger number of patients (n 167, 63.5%) had delirium after a week of palliative care. Patients with delirium are likely to be older, to have a lower Karnofsky level at T0, and to be home care patients. At T0, weakness, nausea, drowsiness, lack of appetite, and well-being are associated with delirium. At T7, weakness, poor appetite, and poor well-being are significantly associated with delirium. 27% of patients who had a normal cognitive status at T0 developed delirium at T7. In patients with delirium, an improvement in the cognitive status corresponds to a significant improvement in weakness, depression, and appetite. Conversely, the occurrence of delirium in patients who had a normal cognitive status at admission significantly increases the level depression, while the level of weakness and appetite decrease. Symptom expression is amplified in patients with delirium admitted to home care or hospices, while patients without delirium can be more responsive to palliative treatments with a significant decrease in intensity of ESAS items.

Systematic vs. on-demand early palliative care in gastric cancer patients: a randomized clinical trial assessing patient and healthcare service outcomes.

PURPOSE: Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer. METHODS: In this prospective, multicenter study, 186 advanced gastric cancer patients were randomized 1:1 to receive standard cancer care (SCC) plus on-demand EPC (standard arm) or SCC plus systematic EPC (interventional arm). Primary outcome was a change in QoL between randomization (T0) and T1 (12 weeks after T0) in the Trial Outcome Index (TOI) scores evaluated through the Functional Assessment of Cancer Therapy-Gastric questionnaire. Secondary outcomes were patient mood, overall survival, and family satisfaction with healthcare and care aggressiveness. RESULTS: The mean change in TOI scores from T0 to T1 was - 1.30 (standard deviation (SD) 20.01) for standard arm patients and 1.65 (SD 22.38) for the interventional group, with a difference of 2.95 (95% CI - 4.43 to 10.32) (p = 0.430). The change in mean Gastric Cancer Subscale values for the standard arm was 0.91 (SD 14.14) and 3.19 (SD 15.25) for the interventional group, with a difference of 2.29 (95% CI - 2.80 to 7.38) (p = 0.375). Forty-three percent of patients in the standard arm received EPC. CONCLUSIONS: Our results indicated a slight, albeit not significant, benefit from EPC. Findings on EPC studies may be underestimated in the event of suboptimally managed issues: type of intervention, shared decision-making process between oncologists and PC physicians, risk of standard arm contamination, study duration, timeliness of assessment of primary outcomes, timeliness of cohort inception, and recruitment of patients with a significant symptom burden. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01996540).

Can early palliative care with anticancer treatment improve overall survival and patient-related outcomes in advanced lung cancer patients? A review of the literature.

PURPOSE: Metastatic non-small-cell lung cancer (NSCLC), the leading cause of death from cancer worldwide, is a debilitating disease that results in a high burden of symptoms and poor quality of life; the estimated prognosis after the diagnosis has been established was less than 1 year until some years ago. At the present, the new targeted therapies and immunotherapy are changing the course of the disease. However, advanced NSCLC remains an incurable disease, with a poor prognosis for the majority of the affected patients, so that quality of life and relief from symptoms are primary objectives of treatment. Some evidences suggest that early palliative care (EPC) for these patients can improve quality of life and even survival. DESIGN: A systematic review of the studies evaluating the impact on objective and on patient-reported outcomes of the introduction of EPC in opposition to standard care (SC), for advanced lung cancer patients, was performed. Because of the small number of studies conducted in this area, retrospective studies were also considered for the review. RESULTS: Five studies were included because they matched the inclusion criteria previously defined as relevant for the study. The review found that both survival and quality of life were better for patients included in EPC groups. CONCLUSIONS: While results of the studies included in this review are not always comparable because different methods and scales have been used, there is enough evidence for clinical oncologists to implement the use of EPC in clinical practice for advanced lung cancer patients.

The challenge of sustainability in healthcare systems: frequency and cost of diagnostic procedures in end-of-life cancer patients.

BACKGROUND: Literature data on the overuse and misuse of diagnostic procedures leading to end-of-life aggressiveness are scarce due to the limited amount of estimated economic waste. This study investigated the potential overuse of diagnostic procedures in a population of end-of-life patients. METHODS: This is a retrospective study on consecutive advanced patients admitted into two Italian hospices. Frequency and relative costs of X-ray imaging, CT scans, MRI, and interventional procedures prescribed in the 3 months before admission were collected in patient electronic charts and/or in administrative databases. We conducted a deeper analysis of 83 cancer patients with a diagnosis of at least 1 year before admission to compare the number of examinations performed at two distant time periods. RESULTS: Out of 541 patients, 463 (85.6%) had at least one radiological exam in the 3 months before last admission. The mean radiological exam number was 3.9 ± 3.2 with a relative mean cost of 278.60 ± 270.20 € per patient with a statistically significant (p < 0.001) rise near death. In the 86-patient group, a higher number of procedures was performed in the last 3 months of life than in the first quarter of the year preceding last admission (38.43 ± 28.62 vs. 27.95 ± 23.21, p < 0.001) with a consequent increase in cost. CONCLUSIONS: Patients nearing death are subjected to a high level of "diagnostic aggressiveness." Further studies on the integration of palliative care into the healthcare pathway could impact the appropriateness of interventions, quality of care, and, ultimately, estimated costs.

The prevalence of constipation at admission and after 1 week of palliative care: a multi-center study.

AIM: To assess the prevalence and intensity of constipation in advanced-cancer patients referred to palliative care, and to assess changes after 1 week of specialist palliative care. METHODS: This was a prospective multi-center study in advanced patients for a period of 1 year. At admission (T0), age, gender, primary tumor, concomitant diseases, Karnofsky status, Palliative prognostic score (PaP), Edmonton Symptom Assessment scale (ESAS), Memorial Delirium Assessment Scale (MDAS), and bowel function index (BFI) were collected. In BFI, high values represent severe constipation. The use of medication was also recorded, as well as possible causes of constipation. The same parameters were recorded 1 week after admission for palliative care (T7). RESULTS: A total of 246 patients were screened for constipation. The mean BFI at T0 was 42.4 (SD = 26.92). One hundred and sixty-three patients (66.3%) had a BFI >28. The mean BFI at T7 was 35.7 (SD = 28.8), with a significant decrease from T0 to T7 (p = .000). A significant decrease of BFI in patients with a BFI >28 was reported (p = .000). In patients with a BFI ≤28 there was a significant worsening of constipation (p = .000). In patients with a BFI >28 at T0 there was a significant increase in the use of laxatives at T7 in comparison with patients having a BFI ≤28 (p = .002). In patients with a BFI ≤28 at T0, who had a significant worsening of BFI (Δ > 12), the use of laxatives was significantly lower in comparison to patients who had a BFI >28 (p = .000). In the multivariate analysis, dehydration and the use of benzodiazepines were independently associated with higher BFI scores. CONCLUSION: Constipation is present in approximately two-thirds of patients, and is principally associated with dehydration and the use of benzodiazepines. Patients with normal bowel function at initial assessment may see a worsening in their condition a week later due to lack of prevention or subsequent under-treatment.

Prevalence of delirium in advanced cancer patients in home care and hospice and outcomes after 1 week of palliative care.

AIM: The aim of this study was to assess the prevalence of delirium in advanced cancer patients admitted to different palliative care services in Italy and possible related factors. The secondary outcome was to assess the changes of delirium after 1 week of palliative care. METHODS: A consecutive sample of patients was screened for delirium in period of 1 year in seven palliative care services. General data, including primary tumor, age, gender, concomitant disease, palliative prognostic score (PaP), and Karnofsky status, were collected. Possible causes or factors associated with delirium were looked for. The Edmonton Symptom Assessment Scale was used to assess physical and psychological symptoms and the Memorial Delirium Assessment Scale (MDAS) to assess the cognitive status of patients, at admission (T0) and 1 week after palliative care (T7). RESULTS: Of 848 patients screened, 263 patients were evaluated. Sixty-six patients had only the initial evaluation. The mean Karnofsky status was 34.1 (SD = 6.69); the mean PaP score at admission was 6.9 (SD = 3.97). The mean duration of palliative care assistance, equivalent to survival, was 38.4 days (SD = 48, range 2-220). The mean MDAS values at admission and after 1 week of palliative care were 6.9 (SD = 6.71) and 8.8 (SD = 8.26), respectively. One hundred ten patients (41.8%) and 167 patients (67.3%) had MDAS values ≥ 7 at admission and after 1 week of palliative care, respectively. Age, dehydration, cachexia, chemotherapy in the last three months, and intensity of drowsiness and dyspnea were independently associated with a MDAS > 7. A worsening of drowsiness, the use of opioids, and the use of corticosteroids were independently associated with changes of MDAS from T0 to T7. CONCLUSION: Although the prevalence of delirium seems to be similar to that reported in other acute settings, delirium tended to worsen or poorly responded to a palliative care treatment. Some clinical factors were independently associated with delirium. This information is relevant for decision-making when delirium does not change despite a traditional intervention. Continuous assessment of delirium should be performed in these settings to detect deterioration of cognitive function. Further studies should elucidate whether an earlier approach to palliative care would decrease the prevalence of delirium at a late stage of disease.

Radiological exams on end-stage oncologic patients before hospice admission.

PURPOSE: To evaluate frequency, type, and cost of diagnostic and interventional radiological exams performed on end-stage oncologic patients in the 90 days before Hospice admission. MATERIALS AND METHODS: Data of patients admitted to Hospice from January 2012 through June 2013 (18 months) were cross-checked with data from the digital archive of the Radiology Department. Frequency and type of exams performed before admission were analyzed across three 1-month periods, namely M-3, M-2, M-1, corresponding to 90-61, 60-31 and 30-1 days before admission. The Regional Range of Fees was used to determine the costs. RESULTS: A total of 389 patients were admitted to Hospice. Before admission, 335 patients (86%) underwent 1543 radiological exams: 919 X-rays, 555 CTs, 39 MRs, and 30 interventional procedures. The cost of these services was € 106,988 (€ 19,918 for X-rays, € 73,956 for CTs, € 9502 for MRs, and € 3612 for interventional procedures). Across the pre-Hospice periods, the proportions of examined patients increased as admission approached: 36% in M-3, 43% in M-2 (P = .038), 65% in M-1 (P < .001). The mean number of exams increased significantly, too (P < .001). CONCLUSIONS: A substantial number of end-stage oncologic patients underwent radiological exams in the 90 days before Hospice admission, and these numbers grew as Hospice access approached. In the end-of-life span, diagnostic excesses should be avoided.

Systematic versus on-demand early palliative care: results from a multicentre, randomised clinical trial.

BACKGROUND: Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating EPC has yet to be defined. METHODS: This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive 'standard cancer care plus on-demand EPC' (n = 100) or 'standard cancer care plus systematic EPC' (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy - Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. FINDINGS: The mean changes in TOI score and HCS score between T0 and T1 were -4.47 and -0.63, with a difference between groups of 3.83 (95% confidence interval [CI] 0.10-7.57) (p = 0.041), and -2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40-4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. INTERPRETATIONS: Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC.

Ultrasound guidance reduces pneumothorax rate and improves safety of thoracentesis in malignant pleural effusion: report on 445 consecutive patients with advanced cancer.

BACKGROUND: Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients, and thoracentesis is an essential procedure in an attempt to delineate the etiology of the fluid collections and to relieve symptoms in affected patients. One of the most common complications of thoracentesis is pneumothorax, which has been reported to occur in 20% to 39% of thoracenteses, with 15% to 50% of patients with pneumothorax requiring tube thoracostomy.The present study was carried out to assess whether thoracenteses in cancer patients performed with ultrasound (US) guidance are associated with a lower rates of pneumothorax and tube thoracostomy than those performed without US guidance. METHODS: A total of 445 patients were recruited in this retrospective study. The medical records of 445 consecutive patients with cancer and MPE evaluable for this study, undergoing thoracentesis at the Oncology-Hematology and Internal Medicine Departments, Piacenza Hospital (Italy) were reviewed. RESULTS: From January 2005 to December 2011, in 310 patients (69.66%) thoracentesis was performed with US guidance and in 135 (30.34%) without it. On post-thoracentesis imaging performed in all these cases, 15 pneumothoraces (3.37%) were found; three of them (20%) required tube thoracostomy. Pneumothorax occurred in three out of 310 procedures (0.97%) performed with US guidance and in 12 of 135 procedures (8.89%) performed without it (P<0.0001). It must be emphasized that in all three patients with pneumothorax requiring tube thoracostomy, thoracentesis was performed without US guidance. CONCLUSIONS: The routine use of US guidance during thoracentesis drastically reduces the rate of pneumothorax and tube thoracostomy in oncological patients, thus improving safety as demonstrated in this study.

Ultrasound-guided central venous catheterization in cancer patients improves the success rate of cannulation and reduces mechanical complications: a prospective observational study of 1,978 consecutive catheterizations.

BACKGROUND: A central venous catheter (CVC) currently represents the most frequently adopted intravenous line for patients undergoing infusional chemotherapy and/or high-dose chemotherapy with hematopoietic stem-cell transplantation and parenteral nutrition. CVC insertion represents a risk for pneumothorax, nerve or arterial punctures. The aim of this prospective observational study was to explore the safety and efficacy of CVC insertion under ultrasound (US) guidance and to confirm its utility in clinical practice in cancer patients. METHODS: Consecutive adult patients attending the oncology-hematology department were eligible if they had solid or hematologic malignancies and required CVC insertion. Four types of possible complication were defined a priore: mechanical, thrombotic, infection and malfunctioning. The patient was placed in Trendelenburg's position, a 7.5 MHZ puncturing US probe was placed in the supraclavicular site and a 16-gauge needle was advanced under real-time US guidance into the last portion of internal jugular vein. The Seldinger technique was used to place the catheter, which was advanced into the superior vena cava until insertion into right atrium. Within two hours after each procedure, an upright chest X-ray and ultrasound scanning were carried out to confirm the CVC position and to rule out a pneumotorax. CVC-related infections, symptomatic vein thrombosis and malfunctioning were recorded. RESULTS: From December 2000 to January 2009, 1,978 CVC insertional procedures were applied to 1,660 consecutive patients. The procedure was performed 580 times in patients with hematologic malignancies and 1,398 times those with solid tumors. A single-needle puncture of the vein was performed on 1,948 of 1,978 procedures (98.48%); only eighteen attempts among 1,978 failed (0.9%). No pneumotorax, no major bleeding, and no nerve puncture were reported; four cases (0.2%) showed self-limiting hematomas. The mean lifespan of CVC was 189.7 +/- 18.6 days (range 7-701). Symptomatic deep-vein thrombosis of the upper limbs developed in 48 patients (2.42%). Catheter-related infections occurred in 197 (9.96%) of the catheters inserted. They were successfully treated with antibiotics and only in 48 (2.9%) patients definitive CVC removal was required for infection and/or thrombosis or malfunctioning. CONCLUSIONS: This study represents the largest published series of consecutive patients with cancer undergoing CVC insertion under US guidance; this procedure allowed the completion of the therapeutic program for 1,930/1,978 (97.6%) of the catheters inserted. The absence of pneumotorax and other major complications indicates that US guidance should be mandatory for CVC insertion in patients with cancer.

Osteonecrosis of the jaw. A newly emerging site-specific osseous pathology in patients with cancer treated with bisphosphonates. Report of five cases and review of the literature.

BACKGROUND: Bisphosphonates are commonly used as standard care in the management of patients with advanced-stage cancer involving bone. There has recently been growing concern that the use of bisphosphonates is associated with osteonecrosis of the jaw (ONJ). METHODS: Between 2001 and 2005, five patients with ONJ associated with pamidronate and zoledronate therapy were diagnosed at our department. The patients had breast cancer, renal carcinoma, mesothelioma, and multiple myeloma, all involving bone. The literature was reviewed. RESULTS: The duration of bisphosphonate therapy before presentation of ONJ ranged from 21 to 36 months. The lesions were localized to the mandible (n=3) and maxilla (n=2). All of the patients presented with pain and exposed bone; in two of them, symptoms began after tooth extraction. A review of the literature through March 2006 identified more than 250 reported cases of ONJ. CONCLUSIONS: The findings in our patients, combined with the literature review, suggest that: (1) the most common clinical presentation of ONJ is pain and exposed bone of the mandible or maxilla; (2) for patients who develop ONJ, conservative, non-surgical treatment is strongly recommended; (3) clinical dental examination and a panoramic jaw radiograph should be performed before patients begin bisphosphonate therapy; (4) dental treatment and other oral procedures should be completed before initiating bisphosphonate therapy; (5) patients should be informed and instructed on the importance of maintaining good oral hygiene and having regular dental assessment; and (6) the medical community needs to be aware of the association between bisphosphonate usage and ONJ so that unnecessary and harmful surgical procedures can be avoided.

Post-traumatic glioma: report of two cases.

We report two cases of brain glioma that developed in the scar of an old brain trauma. The first is that of a 40-year-old man who presented with severe headaches; CT and MRI showed a large mass in the right parietal region. The tumor was unresectable and surgical biopsy showed a glioblastoma multiforme. The patient had suffered a cranial trauma in a road accident 20 years previously with an intrathecal hematoma in the right parietal region. The second case concerns a 60-year-old man who, 15 years after severe head injury in a road accident, developed a glioblastoma multiforme which was localized in the scar of the brain contusion. These cases fulfill the established criteria for a traumatic origin of brain tumors and add further support to the relationship between cranial trauma and the onset of glioma. As stated by other authors, an association between head trauma and brain tumor risk cannot be ruled out and should be studied further.

Weekly docetaxel and gemcitabine following docetaxel plus epirubicin or vinorelbine as first-line treatment of metastatic breast cancer: results of a multicenter phase II study.

AIMS AND BACKGROUND: Sequential docetaxel and gemcitabine following initial docetaxel plus epirubicin or vinorelbine association could be worthwhile as first-line treatment of metastatic breast cancer. METHODS: Fifty-eight patients entered a phase II study that included two sequential phases. In the first phase, 36 and 22 patients previously unexposed or exposed to adjuvant anthracyclines received the association of docetaxel (75 mg/m2, day 1) with epirubicin (75 mg/m2, day 1) or vinorelbine (20 mg/m2, days 1 and 5), respectively, every 21 days for 4 courses. In the second phase, patients who had a response (R) or stable disease (SD) received docetaxel (35 mg/m2) and gemcitabine (800 mg/m2) on days 1, 8 and 15 every 28 days for 4 courses. RESULTS: In the first phase, grade > or = III neutropenia occurred in 51% and 37% of patients during docetaxel-epirubicin and docetaxel-vinorelbine, respectively. In the second phase, it occurred in the 27% and 15% of patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine, respectively. On an intention to treat basis, the complete (CR) + partial response (PR) rate to the first phase was 71%, and 22% of patients had SD, without a significant difference between the docetaxel-epirubicin and docetaxel-vinorelbine arms. After the second phase, the CR + PR rate was 65%, and 14% of patients had SD. Median time to progression and survival were 12.1 and 22.0 months, respectively, without a significant difference between patients initially treated with docetaxel-epirubicin and docetaxel-vinorelbine. CONCLUSIONS: Following an initial docetaxel-based treatment, weekly docetaxel and gemcitabine maintains high percentages of R and SD, with improved toxicity. Survival was similar in patients previously untreated and treated with adjuvant anthracyclines.

[Thrombotic thrombocytopenic purpura: report of seven cases]. / Porpora trombotica trombocitopenica: descrizione di sette casi.

From May 1999 to January 2002 we observed 7 patients (4 females and 3 males, median age 55 years, range 31-81 years) with thrombotic thrombocytopenic purpura (TTP). Six patients has been previously undiagnosed and 1 patient was at second relapse. Trigger factors of TTP were identified in 6 patients: ticlopidine treatment (2 patients); an acute cutaneous infection episode immediately before the features of TTP (1 patient); presence of devices: orthodontic (1 patient) and intrauterine contraceptive (1 patient), Mycoplasma urealyticum vaginal infection (1 patient). In all the 7 patients the clinical status was mainly related to the hemolytic anemia, thrombocytopenia and neurological events. One of these patients presented with hemolytic-uremic syndrome with acute renal failure and macrohematuria at onset, another one showed a systemic exanthema post-infection-like. Six out of 7 patients presented with different neurological events: headache, confusion, focal neurological failure. All the 7 patients were promptly treated with plasma-exchange and cryosupernatant plasma infusion. In addition they received prednisone 25-50 mg/day. All the 7 patients achieved a complete remission after plasma-exchange, one relapsed 3 months later and was treated with plasma-exchange again. All the patients are in complete remission with a median follow-up of 36.3 months (range 20-62 months). From these cases we suggest: 1) clinicians should take in mind the suspicion of TTP in every patient with hemolytic, negative direct Coombs test, anemia, thrombocytopenia, high level of lactate dehydrogenase; 2) the treatment of choice is plasma-exchange; 3) the response of treatment is good if therapy is promptly and aggressively administered; 4) the possible role of a trigger factor for removing it and to prevent relapses.