Thoracic Radiotherapy in Extensive Disease Small Cell Lung Cancer: Multicenter Prospective Observational TRENDS Study.

(1) Introduction: Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods: This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results: From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42-81); 38 patients (59%) were male and 26 (41%) female. Carboplatin + etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients; it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions: Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC.

Safety of Inhomogeneous Dose Distribution IMRT for High-Grade Glioma Reirradiation: A Prospective Phase I/II Trial (GLIORAD TRIAL).

Glioblastoma multiforme (GBM) is the most aggressive astrocytic primary brain tumor, and concurrent temozolomide (TMZ) and radiotherapy (RT) followed by maintenance of adjuvant TMZ is the current standard of care. Despite advances in imaging techniques and multi-modal treatment options, the median overall survival (OS) remains poor. As an alternative to surgery, re-irradiation (re-RT) can be a therapeutic option in recurrent GBM. Re-irradiation for brain tumors is increasingly used today, and several studies have demonstrated its feasibility. Besides differing techniques, the published data include a wide range of doses, emphasizing that no standard approach exists. The current study aimed to investigate the safety of moderate-high-voxel-based dose escalation in recurrent GBM. From 2016 to 2019, 12 patients met the inclusion criteria and were enrolled in this prospective single-center study. Retreatment consisted of re-irradiation with a total dose of 30 Gy (up to 50 Gy) over 5 days using the IMRT (arc VMAT) technique. A dose painting by numbers (DPBN)/dose escalation plan were performed, and a continuous relation between the voxel intensity of the functional image set and the risk of recurrence in that voxel were used to define target and dose distribution. Re-irradiation was well tolerated in all treated patients. No toxicities greater than G3 were recorded; only one patient had severe G3 acute toxicity, characterized by muscle weakness and fatigue. Median overall survival (OS2) and progression-free survival (PFS2) from the time of re-irradiation were 10.4 months and 5.7 months, respectively; 3-, 6-, and 12-month OS2 were 92%, 75%, and 42%, respectively; and 3-, 6-, and 12-month PFS2 were 83%, 42%, and 8%, respectively. Our work demonstrated a tolerable tolerance profile of this approach, and the future prospective phase II study will analyze the efficacy in terms of PFS and OS.

Efficacy and safety of a colostrum- and Aloe vera-based oral care protocol to prevent and treat severe oral mucositis in patients undergoing hematopoietic stem cell transplantation: a single-arm phase II study.

Oral mucositis is one of the worst effects of the conditioning regimens given to patients undergoing hematopoietic stem cell transplantation. It is characterized by dry mouth, erythema, mucosal soreness, ulcers, and pain, and it may impact patient outcomes. Bovine colostrum and Aloe vera contain a wide variety of biologically active compounds that promote mucosal healing. A non-randomized phase II study was designed to assess the safety and efficacy of a combined bovine colostrum and Aloe vera oral care protocol to prevent and to treat severe oral mucositis in transplant patients. Two commercially available products were given to patients in addition to the standard protocol: Remargin Colostrum OS® mouthwash and Remargin Colostrum Gastro-Gel® taken orally. Forty-six (78.0%) patients experienced oral mucositis, 40 (67.8%) developed mild-moderate forms, and 6 (10.2%) severe ones. Comparing the study group's outcomes with those of a homogeneous historical control group, severe oral mucositis decreased significantly (10.2% vs. 28.4%; P < 0.01), as did its duration (0.5 ± 1.9 vs. 1.5 ± 3.0 days; P < 0.01). Febrile neutropenia episodes (69.5% vs. 95.1%; P < 0.01) and duration (4.0 ± 4.7 vs. 6.2 ± 4.5 days; P < 0.01) also decreased. These findings show that the experimental protocol seems effective in preventing severe forms of oral mucositis. However, a randomized controlled trial is necessary to confirm this.

Stem cell transplantation patients receiving a novel oral care protocol for oral mucositis prevention and treatment: patient-reported outcomes and quality of life.

BACKGROUND: Oral mucositis (OM) is one of the most debilitating effects of toxicity due to hematopoietic stem cell transplantation (HSCT) conditioning regimens. The aim of this secondary analysis of the data of a phase II study designed to assess the efficacy of a novel oral care protocol containing bovine colostrum and aloe vera to prevent oral mucositis was to compare outcomes reported by patients with those collected by healthcare professionals (HCPs). METHOD: Data on oral mucositis severity, duration, time of onset and related pain were collected from patients using the Oral Mucositis Daily Questionnaire (OMDQ). HCPs assessed the same outcomes using the World Health Organization oral mucositis scale and pain numerical rating scale. Quality of life was assessed with the 3-level EuroQol-5 dimensions. RESULTS: Fifty-nine autologous/allogeneic graft patients were recruited, 46 of whom (78.0%) experienced OM. Mean onset was 9.1 (SD ± 3.5) days after conditioning initiation, mean duration was 10.4 (SD ± 4.3) days, and the average maximum pain score was 3.7 (SD ± 2.7). Self-administration of the OMDQ detected oral symptoms at least 1 day sooner compared to objective assessments (p = 0.025). Significant differences were observed between the patient-reported and the HCP-assessment data on oral mucositis severity grading distribution (p < 0.0001) and highest pain score (p < 0.0001). Quality of life score variations were correlated with changes in oral mucositis severity during patients' hospital stay. CONCLUSIONS: Further studies are necessary to improve the understanding of these findings; a randomised controlled trial is being set up at our institution.

Intravenous methylprednisolone pulses in hospitalised patients with severe COVID-19 pneumonia: a double-blind, randomised, placebo-controlled trial.

RATIONALE: Pulse glucocorticoid therapy is used in hyperinflammation related to coronavirus disease 2019 (COVID-19). We evaluated the efficacy and safety of pulse intravenous methylprednisolone in addition to standard treatment in COVID-19 pneumonia. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, 304 hospitalised patients with COVID-19 pneumonia were randomised to receive 1 g of methylprednisolone intravenously for three consecutive days or placebo in addition to standard dexamethasone. The primary outcome was the duration of patient hospitalisation, calculated as the time interval between randomisation and hospital discharge without the need for supplementary oxygen. The key secondary outcomes were survival free from invasive ventilation with orotracheal intubation and overall survival. RESULTS: Overall, 112 (75.4%) out of 151 patients in the pulse methylprednisolone arm and 111 (75.2%) of 150 in the placebo arm were discharged from hospital without oxygen within 30 days from randomisation. Median time to discharge was similar in both groups (15 days, 95% CI 13.0-17.0 days and 16 days, 95% CI 13.8-18.2 days, respectively; hazard ratio (HR) 0.92, 95% CI 0.71-1.20; p=0.528). No significant differences between pulse methylprednisolone and placebo arms were observed in terms of admission to intensive care unit with orotracheal intubation or death (20.0% versus 16.1%; HR 1.26, 95% CI 0.74-2.16; p=0.176) or overall mortality (10.0% versus 12.2%; HR 0.83, 95% CI 0.42-1.64; p=0.584). Serious adverse events occurred with similar frequency in the two groups. CONCLUSIONS: Methylprenisolone pulse therapy added to dexamethasone was not of benefit in patients with COVID-19 pneumonia.

[Descriptive analytical study on patient mobilization of the Internal Medicine Department of the USL - IRCCS of Reggio Emilia (MOBINT)]. / Studio analitico descrittivo sulla mobilizzazione dei pazienti del Dipartimento Internistico dell'Azienda USL ­ IRCCS di Reggio Emilia (MOBINT).

INTRODUCTION: Hospitalisation represents a significant risk factor for the decline in the general conditions of the elderly. Loss of autonomy in elderly inpatients, together with immobilisation, has been defined as 'Hospital-Acquired Disability' and affects 65% of this class of patients. Less than half of them will regain independent mobilisation. Included among the negative effects are: falls, increased percentage of admission to nursing homes, longer hospital admissions, increased mortality and morbitity. Despite these facts, elderly patients remain in bed for 83-95% of their hospital stay; they rarely walk or are mobilised. Only on an international level has this issue been analysed OBJECTIVES: To analyse active mobilisation in inpatients. METHODS: Prospective analytical and descriptive study performed from December 2018 - May 2019 in the Clinical Medicine department of the AUSL of Reggio Emilia. Descriptive analysis of the data has been performed. RESULTS: A total of 1725 patients were screened for the study. After applying the inclusion criteria, 295 patients were enrolled in the study, 9 of which were then excluded for failure to be mobilised. 66.4% of these patients were mobilized the morning during hygiene-rounds. According to the nurse, they appeared in a stable state, alert and oriented (88.1%) and used a variety of aids (from 1 to 3) (57.3%). The frequency of mobilisations were: 44.4% once a day, 31.2% twice, 24.4% three times or more. DISCUSSION: This study highlighted that mobilisation is strictly correlated to first assistance, frequently relying on health care assistants, and is mostly applied to oriented patients who only need one assistant. Further studies are required to investigate connections between patient's features and mobilisation.

Postoperative hypoparathyroidism after completion thyroidectomy for well-differentiated thyroid cancer.

OBJECTIVE: Thyroid surgery may lead to postoperative complications. The aim of this paper was to determine whether the rate of postoperative hypoparathyroidism (HPT) is influenced by whether surgery is staged. DESIGN: Single-institution retrospective observational study. METHODS: The clinical records of 786 patients treated at the Otolaryngology Unit of the Azienda USL-IRCCS di Reggio Emilia between January 1990 and December 2015 were reviewed. Patients were divided into two groups according to the surgical treatment received: group TT (637 patients, 81.04%) underwent single-stage total thyroidectomy; Group cT (149 patients, 18.96%) underwent loboisthmusectomy and delayed completion total thyroidectomy. Transient and permanent HPT, assessed after 6 months of follow-up, were the primary endpoints. Risk factors of postoperative HPT were also analysed as secondary outcomes. RESULTS: Rates of transient HPT in group TT were higher than those observed in group cT, (P = 0.0057). Analysis of risk factors identified sex as an independent risk factor for transient HPT only for group TT (P = 0.0012) and the number of parathyroid glands remaining in situ (PGRIS) as an independent risk factor for transient and permanent HPT for group TT (P < 0.0001 and P = 0.0002, respectively). CONCLUSIONS: This study suggests that the risk of transient postoperative HPT is lower in patients that undergo completion thyroidectomy. Further independent risk factors for postoperative HPT are female sex and PGRIS score. In light of the growing use of conservative surgery for thyroid neoplasms, these findings could help to adequately plan surgery in order to reduce endocrine complications.

Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: The coronavirus disease 2019 (COVID-19) pandemic is threatening billions of people worldwide. Tocilizumab has shown promising results in retrospective studies in patients with COVID-19 pneumonia with a good safety profile. Objective: To evaluate the effect of early tocilizumab administration vs standard therapy in preventing clinical worsening in patients hospitalized with COVID-19 pneumonia. Design, Setting, and Participants: Prospective, open-label, randomized clinical trial that randomized patients hospitalized between March 31 and June 11, 2020, with COVID-19 pneumonia to receive tocilizumab or standard of care in 24 hospitals in Italy. Cases of COVID-19 were confirmed by polymerase chain reaction method with nasopharyngeal swab. Eligibility criteria included COVID-19 pneumonia documented by radiologic imaging, partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2/Fio2) ratio between 200 and 300 mm Hg, and an inflammatory phenotype defined by fever and elevated C-reactive protein. Interventions: Patients in the experimental arm received intravenous tocilizumab within 8 hours from randomization (8 mg/kg up to a maximum of 800 mg), followed by a second dose after 12 hours. Patients in the control arm received supportive care following the protocols of each clinical center until clinical worsening and then could receive tocilizumab as a rescue therapy. Main Outcome and Measures: The primary composite outcome was defined as entry into the intensive care unit with invasive mechanical ventilation, death from all causes, or clinical aggravation documented by the finding of a Pao2/Fio2 ratio less than 150 mm Hg, whichever came first. Results: A total of 126 patients were randomized (60 to the tocilizumab group; 66 to the control group). The median (interquartile range) age was 60.0 (53.0-72.0) years, and the majority of patients were male (77 of 126, 61.1%). Three patients withdrew from the study, leaving 123 patients available for the intention-to-treat analyses. Seventeen patients of 60 (28.3%) in the tocilizumab arm and 17 of 63 (27.0%) in the standard care group showed clinical worsening within 14 days since randomization (rate ratio, 1.05; 95% CI, 0.59-1.86). Two patients in the experimental group and 1 in the control group died before 30 days from randomization, and 6 and 5 patients were intubated in the 2 groups, respectively. The trial was prematurely interrupted after an interim analysis for futility. Conclusions and Relevance: In this randomized clinical trial of hospitalized adult patients with COVID-19 pneumonia and Pao2/Fio2 ratio between 200 and 300 mm Hg who received tocilizumab, no benefit on disease progression was observed compared with standard care. Further blinded, placebo-controlled randomized clinical trials are needed to confirm the results and to evaluate possible applications of tocilizumab in different stages of the disease. Trial Registration: ClinicalTrials.gov Identifier: NCT04346355; EudraCT Identifier: 2020-001386-37.

Upright BPPV Protocol: Feasibility of a New Diagnostic Paradigm for Lateral Semicircular Canal Benign Paroxysmal Positional Vertigo Compared to Standard Diagnostic Maneuvers.

Background: The diagnosis of benign paroxysmal positional vertigo (BPPV) involving the lateral semicircular canal (LSC) is traditionally entrusted to the supine head roll test, also known as supine head yaw test (SHYT), which usually allows identification of the pathologic side and BPPV form (geotropic vs. apogeotropic). Nevertheless, SHYT may not always allow easy detection of the affected canal, resulting in similar responses on both sides and intense autonomic symptoms in patients with recent onset of vertigo. The newly introduced upright head roll test (UHRT) represents a diagnostic maneuver for LSC-BPPV, supplementing the already-known head pitch test (HPT) in the sitting position. The combination of these two tests should enable clinicians to determine the precise location of debris within LSC, avoiding disturbing symptoms related to supine positionings. Therefore, we proposed the upright BPPV protocol (UBP), a test battery exclusively performed in the upright position, including the evaluation of pseudo-spontaneous nystagmus (PSN), HPT and UHRT. The purpose of this multicenter study is to determine the feasibility of UBP in the diagnosis of LSC-BPPV. Methods: We retrospectively reviewed the clinical data of 134 consecutive patients diagnosed with LSC-BPPV. All of them received both UBP and the complete diagnostic protocol (CDP), including the evaluation of PSN and data resulting from HPT, UHRT, seated-supine positioning test (SSPT), and SHYT. Results: A correct diagnosis for LSC-BPPV was achieved in 95.5% of cases using exclusively the UBP, with a highly significant concordance with the CDP (p < 0.000, Cohen's kappa = 0.94), regardless of the time elapsed from symptom onset to diagnosis. The concordance between UBP and CDP was not impaired even when cases in which HPT and/or UHRT provided incomplete results were included (p < 0.000). Correct diagnosis using the supine diagnostic protocol (SDP, including SSPT + SHYT) or the sole SHYT was achieved in 85.1% of cases, with similar statistical concordance (p < 0.000) and weaker strength of relationship (Cohen's kappa = 0.80). Conclusion: UBP allows correct diagnosis in LSC-BPPV from the sitting position in most cases, sparing the patient supine positionings and related symptoms. UBP could also allow clinicians to proceed directly with repositioning maneuvers from the upright position.

Hospitalisation and morbidity due to adverse drug reactions in elderly patients: a single-centre study.

BACKGROUND: Adverse drug reaction (ADR) is a leading but under-recognised cause of illness, particularly in frail subjects with multiple comorbidities. AIM: To investigate the frequency, patterns and outcomes of ADR as a cause of hospitalisation in elderly patients admitted to an internal medicine ward. METHODS: We performed a retrospective observational study including every patient aged over 65 years who was admitted to our department during a 12-month period. Patients admitted to short-stay (<24 h) observation unit were excluded. RESULTS: ADR accounted for 106 of total 1750 recorded admissions, which constituted a proportion of 6.1% (95% confidence interval 5.0-7.3%). The median age of patients was 83.5 (78.0-87.0) years and 56.6% were on polypharmacy. A total of 170 ADR was recorded with 45.3% of subjects experiencing concomitantly more than one ADR from a single molecule. Diuretics were the most commonly imputed molecules (30 events, 17.6%), followed by antithrombotics (25 events, 14.7%) and central nervous system-active drugs (16 events, 9.4%). Interactions were judged responsible for 39 cases of ADR (36.8%). An unfavourable outcome was observed in about one-third of patients (37.7%). Among those subjects, 11 (10.4%) died and 29 (27.4%) had residual disability. CONCLUSION: ADR are a common cause of hospital admission in elderly patients and are often associated with adverse outcomes. Our data underline the need of appropriate strategies aimed at identifying high-risk patients and avoiding potentially preventable drug toxicities.

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.

Pei regimen: a therapeutic option in small cell lung cancer? A retrospective monoinstitutional analysis of 46 consecutive cases.

OBJECTIVES: Combination chemotherapy is very active in small cell lung cancer (SCLC), although no improvement in overall survival (OS) has been done in the last 25 years, with Cisplatin-Etoposide (PE) still considered the world-wide standard, with an average median survival of about 7-8 months in patients with extended disease (ED). In 1995, a randomized trial of the Hoosier Group in 171 ED patients showed a significant advantage in overall survival in patients treated with PEI (Cisplatin, Etoposide and Ifosfamide), compared to PE. Despite that, PEI regimen has not become a commonly used regimen in SCLC. MATERIALS AND METHODS: Here we present a retrospective analysis of 46 consecutive patients (30 males and 16 females) with SCLC that were treated at our Institution with PEI regimen: Cisplatin 20 mg/m2, Etoposide 75 mg/m2 and Ifosfamide 1200 mg/m2, day 1 to 4, every 3 weeks. Patients received a total of 219 cycles of chemotherapy, with a mean of 4,7 cycles per patient. Median age was 63 (range 59-70); performance status (PS) was 0 in 29 patients (63%), 1 in 13 patients (28%) and 2 in 4 patients (9%). RESULTS: In 19 limited disease (LD) patients partial response (PR) rate was 74%, and complete response (CR) was 16%. In 27 ED patients we observed 63% of PR and 26% of CR. Median time to progression (TTP) was 15.2 months in LD and 7.1 months in ED with median overall survival (OS) of 28.2 and 11.8 months, respectively. Toxicity was manageable, with a high dose intensity. CONCLUSIONS: PEI regimen, in our opinion, may be a possible therapeutic option, with high activity and an acceptable toxicity profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02324296 . INSTITUTIONAL REVIEW BOARD THAT APPROVED THE STUDY: Institutional review board of Reggio Emilia, Azienda Ospedaliera S.Maria Nuova/IRCCS.

In vivo analysis of the iris thickness by spectral domain optical coherence tomography.

PURPOSE: To assess the effectiveness of spectral domain optical coherence tomography (SD-OCT) in providing in vivo measurements of iris thickness in healthy and pathological subjects. METHODS: 14 healthy volunteers and 14 patients with unilateral Fuchs' uveitis were enrolled in the study. The two groups were comparable for age, gender and race. Each subject underwent complete clinical examination and anterior segment SD-OCT imaging in both eyes. SD-OCT scans of the iris were performed following a cross-sectional pattern. Iris thickness values were obtained using a purposely developed software-based analysis of OCT images. Measurements were carried out twice by two trained independent operators to assess intraobserver and interobserver repeatability. Analysis of iris thickness was conducted in four main quadrants: superior, inferior, nasal and temporal. Iris thickness values from normal subjects were compared with the ones measured in the affected and fellow eyes of patients with Fuchs' uveitis. RESULTS: Iris thickness measurements showed good intraobserver and interobserver repeatability (intraclass correlation coefficient >0.971). Superior and temporal iris sectors showed respectively thickest and thinnest values in all groups. In healthy eyes, iris thickness ranged from 327.92±37.29 µm temporally to 405.25±48.49 µm superiorly. Iris thickness measurements in the affected eyes of Fuchs' uveitis patients ranged from 285.48±56.02 µm temporally to 376.12±60.97 µm superiorly. Multiple comparison analysis showed iris thickness values to be significantly lower in eyes affected by Fuchs' uveitis than both in fellow eyes (p<0.001) of the same patients and in healthy eyes (p=0.0074). CONCLUSIONS: SD-OCT is a suitable technique for iris thickness assessment. Thickness analysis must be carried out using a sectorial approach, taking into consideration anatomical variations existing between different iris regions. SD-OCT is a potentially useful tool for detecting iris thickness variations induced by pathological conditions such as Fuchs' uveitis.

Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: the need for further revision of dose and schedule.

Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of 5-fluorouracil (5-FU) and its derivatives (capecitabine and tegafur). Complete or partial deficiency of DPD activity has been demonstrated to induce severe toxicities in cancer patients treated with fluoropyrimidine therapy. We analyzed 180 individuals that were candidates for a treatment with 5-FU class drugs for the most common DPD mutation, IVS14+1G>A, and detected four heterozygous patients. We recorded the toxicities for all 180 individuals after the first two chemotherapy cycles and found that three of the four patients, although they were treated with a dose reduction in 50 % on the basis of the genetic analysis, all showed severe toxicities that resulted in hospitalization of patient and premature discontinuation of treatment. One patient with mutated DPD was not treated with chemotherapy upon the clinician's decision because of his DPD mutated genotype and the presence of microsatellite instability. Our data suggest that greater dose reductions or alternative therapies are needed for patients with DPD IVS14+1G>A mutations.

A longitudinal study of thyroidectomized patients in a region of northern Italy: benign versus malignant disease.

OBJECTIVE: Thyroid disease is very common, particularly nodular goiter. Total thyroidectomy is a therapeutic option for both malignant and benign disease. The aim of the study was to evaluate the number of total thyroidectomy surgeries and the rate of benign and malignant histologic exams over the last decade. METHODS: Hospital discharge records in the Emilia Romagna region (Italy) that reported total thyroidectomy as the principal surgical procedure and included the relative histologic diagnosis were reviewed for the period 2000 to 2010. Mean increment and geometric mean of increments per year were calculated to evaluate differences over the years. RESULTS: More than 25,000 patients underwent total thyroidectomy between 2000 and 2010. The total number of thyroidectomies increased over this period, with a mean increment of 7.16% per year. The percentage of malignancies among the total number of thyroidectomies increased from 26.1% (2000) to 39.9% (2010) (mean increment, 1.38% per year). Nontoxic multinodular goiter was the most frequent diagnosis, accounting for 36% of all thyroidectomies. CONCLUSIONS: Between 2000 and 2010, the proportion of patients thyroidectomized for benign disease progressively decreased, as documented by a lower thyroidectomy/malignancy ratio. Currently, about 60% of thyroid interventions are performed for benign pathology. Improved preoperative diagnostic accuracy and the availability of nonsurgical procedures will presumably further reduce the number of thyroidectomies with benign histologic diagnoses.

[The predictive value of a risk assessment tool for falls in elderly hospitalized patients]. / Determinazione del valore predittivo di una scala di valutazione del rischio di cadute in pazienti anziani ospedalizzati.

AIM: Falls represent a significant problem in acute care settings, and are responsible of severe complications, especially in older adults. Although the literature has suggested a large number of instruments for the assessment of fall risk, their validity is questionable. OBJECTIVE: A prospective cohort study was designed to test the performance of FRASS (Fall Risk Assessment Scoring System) in identifying at risk patients. METHODS AND SUBJECTS: All patients aged > 65 years admitted to seven Medical Units of Bergamo Hospital (Italy) between November 1, 2007 and January 31, 2008 were screened with the FRASS. RESULTS: Falls occurred in 16/564 (2.8%) patients. FRASS sensitivity and specificity were low (50% and 59%, respectively). Since this instrument classifies too many patients who do not fall as at risk, and some patients who fall at no risk, its implementation in our hospital cannot be recommended.

Randomized trial comparing cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with rotational CMF, epirubicin and vincristine as primary chemotherapy in operable breast carcinoma.

BACKGROUND: According to the overview of Early Breast Cancer Trialists' Collaborative Group, anthracycline containing regimens are superior to cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant chemotherapy for breast carcinoma, but no comparative information is available in terms of primary chemotherapy. In the current randomized controlled trial, the authors compared CMF with a chemotherapy regimen including CMF, epirubicin, and vincristine (CMFEV). METHODS: Two hundred eleven patients with Stages I and II palpable breast carcinoma and tumor diameter > 2.5 cm or < or = 2.5 cm with cytologically proven axillary lymph node involvement were randomized to receive CMF (arm A) or CMFEV regimen (arm B) for four cycles before surgery. After surgery, patients in both arms received adjuvant CMF for three cycles; the postmenopausal patients also received tamoxifen for two years. RESULTS: There were no significant differences in the complete response (CR) and in the CR plus partial response (PR) rates between the two arms. In the subset analysis, among premenopausal patients, significantly higher rates of CR (26% vs 4%, P = 0.004) and of CR + PR rates (80% vs 54%, P = 0.007) were observed in the CMFEV, as compared to the CMF arm. Multivariate analysis confirmed the presence of a significant interaction between menopausal status and type of treatment on the probability of achieving CR (P = 0.02) or CR + PR (P = 0.01). There were no major differences in the side effects of the two treatments, with the exception of more frequent alopecia in the experimental arm. CONCLUSIONS: The results of the current study are in line with those of previous published randomized clinical trials comparing regimens without and with anthracycline as adjuvant treatment, indicating an agreement between the short term response to primary chemotherapy and the long term results observed in the adjuvant setting.