Five-year recurrence after endoscopic approach to pilonidal sinus disease: A multicentre experience.

PURPOSE: The aim of this study was to evaluate the 5-year recurrence rate of pilonidal sinus disease (PSD) after endoscopic sinusectomy and identify risk factors for recurrence. METHODS: All consecutive patients from September 2011 through December 2017 who underwent endoscopic sinusectomy at seven referral centres for pilonidal sinus treatment were retrospectively analysed from a prospectively maintained database. RESULTS: Out of 290 patients (185 males versus 105 female, with a mean age of 25.5±6.9), 73 presented recurrence at 5-year follow-up with a recurrence rate of 25.2%. The number of pilonidal sinus with pits off the midline (p = 0.001) and the mean (SD) distance from the most lateral orifice to the midline (p = 0.001) were higher in the group of patients with recurrence at 5-year follow-up. Multivariate analysis demonstrated that the position of the pits off the midline (p = 0.001) and the distance of the most lateral orifice from the midline (p = 0.001) were independent risk factors for recurrence at 5-year follow-up. Receiver operating characteristic (ROC) curve analysis showed that the distance of lateral orifice from midline predicted an 82.2% possibility of recurrence at 5-year follow-up and Youden's test identified the best cut-off as 2 cm for this variable. Out of 195 cases with the most lateral orifice less than 2 cm from the midline, 13 presented recurrence at 5-year follow-up with a recurrence rate of 6.7%. Out of 95 cases with the most lateral orifice more than 2 cm from midline, 60 showed recurrence at 5-year follow-up with a recurrence rate of 63.2%. CONCLUSIONS: This data may help guide which disease characteristics predict the optimal use of an endoscopic pilonidal sinus technique.

Homcology: home chemotherapy delivery in a simultaneous care project for frail advanced cancer patients.

Homcology is a project that represents both an opportunity for patients who may benefit from chemotherapy so far, but present physical and social problems that prevent day-hospital access, and a model of "no-profit" contribution to the Public Health System. Our medical oncology department conducted the project from May 2014 to January 2019. We included frail patients (G-8 < 14), with advanced disease, treated with oral, subcutaneous, or parenteral biological agents, with limitations to day-hospital access, comorbidities, and at least 6-month life expectancy. A multidisciplinary team included three oncologists, four nurses, an anesthetist, a psychologist, and a physiotherapist. Satisfaction was evaluated with FAMCARE scale. A total of 188 patients (median age of 73 years, 38-87) were enrolled. Ninety percent of patients presented with metastatic disease and a median G-8 score of 8.8 (3-13.5). All of them received anticancer treatment and concomitant supportive care; 24 patients received two or more lines of treatment. The median duration of taking care was 175 days (7-1200). A median number of 254 (195-325) nursing and 164 (139-190) medical visits were performed a year, with an average of 1.9 and 1.2 visits a month per patient respectively. The median number of in-line patients was 20 (17-25). Hospitalization occurred in 18% of cases. One-third of them died at home. The others were referred to hospice. Our experience shows that the integration of home cancer treatment and supportive care is effective. Hospitalization rate is lower than data reported in the literature. Results need to be confirmed in prospective pharmacoeconomics studies.

Accuracy of the fluorescence-aided identification technique (FIT) for detecting tooth-colored restorations utilizing different fluorescence-inducing devices: an ex vivo comparative study.

OBJECTIVES: The aim of the present study was to compare the accuracy of the conventional illumination method (CONV) and the fluorescence-aided identification technique (FIT) for distinguishing between composite restorations and intact teeth using different fluorescence-inducing devices commonly used for FIT. MATERIALS AND METHODS: Six groups of six dentists equipped with one of six different FIT systems each independently attempted to identify composite restorations and intact teeth on a full-mouth model with 22 composite restorations using CONV and, 1 h later, FIT. The entire procedure was repeated 1 week later. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values, including 95% confidence intervals (CI), were calculated for CONV and FIT overall and for each device. The influence of examiner age, method, and device on each parameter was assessed by multivariate analysis of variance. RESULTS: The sensitivity (84%, CI 81-86%), specificity (94%, CI 93-96%), PPV (92%, CI 90-94%), and NPV (90%, CI 88-91%) of FIT was significantly higher than that of CONV (47%, CI 44-50%; 82%, CI 79-84%; 66%, CI 62-69%, and 69%, CI 68-71%, respectively; p<0.001). The differences between CONV and FIT were significant for all parameters and FIT systems except VistaCam, which achieved no significant difference in specificity. Examiners younger than 40 years attained significantly higher sensitivity and negative predictive values than older examiners. CONCLUSIONS: FIT is more reliable for detecting composite restorations than the conventional illumination method. CLINICAL RELEVANCE: FIT can be considered an additional or alternative tool for improving the detection of composite restorations.

Exploring potential risk factors of antimicrobial use in beef cattle.

Livestock species are major contributors to the increase of antimicrobial (AM) resistance which is a worldwide concern for both human and animal health. The over-use of AM is widely acknowledged, however, unlike pigs, poultry and dairy cattle, knowledge on potential risk factors affecting AM usage (AMU) in beef industry is limited. Hence, this study aimed to investigate the impact of farm, breed, sex and season of arrival of purchased beef cattle on AMU in Italian beef cattle. Data on 1063 batches were collected from January 2016 to April 2019 from specialised beef fattening farms located in the north of Italy. Information on breed, sex, date of arrival, performance traits and AM agents used on farm was collected, and the treatment incidence 100 (TI100) indexes per batch were calculated using the defined daily dose animal estimated according to Italian summaries of product characteristics. Factors affecting TI100 indexes were investigated using a cross-classified multilevel model. Farms largely differed in terms of AMU. Males had greater AMU than females (P < 0.001), likely due to their higher susceptibility to disease. Statistically significant differences were observed between seasons of arrival with summer and spring having lower TI100 indexes than winter and autumn (P < 0.001). Indeed, winter is commonly linked to an increase in respiratory diseases in beef cattle. Finally, the TI100it indexes tended to be different among breeds with Blonde d'Aquitaine and Limousine having greater AMU compared to the other breeds. Results of this study provided valuable information on potential risk factors of AMU in beef production which may be useful to address its reduction. For instance, the development of tailored management strategies for specific breeds, targeted approaches to improve the health of males as well as greater care towards batches purchased in winter are possible advice to implement on-farm for a more responsible AM stewardship.

Octatropine methyl bromide and diazepam combination (Valpinax) in patients with irritable bowel syndrome: a multicentre, randomized, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and tolerability of octatropine methyl bromide plus diazepam (Valpinax) in patients with irritable bowel syndrome (IBS). MATERIALS AND METHODS: We conducted a randomized, double-blind, multicentre study in 186 patients aged 18-65 years with IBS diagnosed according to Rome II criteria. Following a 2-week washout period, patients received octatropine plus diazepam 40 mg/2.5 mg twice daily or placebo for 6 weeks. The primary efficacy endpoint was response to a weekly question: "did you have satisfactory relief of your abdominal pain and discomfort during the last week?" Other endpoints included abdominal swelling, abdominal pain and discomfort, symptom severity, and the number of bowel movements. A prespecified subgroup analysis was conducted in patients with an abdominal pain and discomfort score > or = 3. RESULTS: The primary efficacy endpoint showed a tendency towards a statistically significant benefit for octatropine plus diazepam over placebo among patients with a baseline abdominal pain and discomfort score of > or = 3 (3 vs. 0 patients; p = 0.059). Octatropine plus diazepam demonstrated significant improvements from baseline in all parameters assessed, but not compared with placebo. Adverse events were reported in 15.1% of patients receiving octatropine plus diazepam. CONCLUSIONS: Patients with IBS and an abdominal pain and discomfort score of > or = 3, who may be considered in the active phase of the disease, may derive some benefits from octatropine plus diazepam. This study highlights that Rome II criteria should be considered with particular care in the design of a clinical trial, since it does not consider disease activity level on admission.

Effect of visual biofeedback cycling training on gait in patients with multiple sclerosis. / Efectos del entrenamiento en bicicleta con retroalimentación visual sobre la marcha en pacientes con esclerosis múltiple.

INTRODUCTION: Gait alterations are present in a high percentage of patients with multiple sclerosis (MS). They appear from early stages of the disease and can limit patients' capacity to perform basic activities of daily living, affecting their quality of life. Visual biofeedback cycling training appears to be a useful tool in treating these impairments. This study aims to evaluate the short-term effect of visual biofeedback cycling training on gait in patients with MS. MATERIAL AND METHODS: A total of 61 patients with mild to moderate MS were randomly assigned to a control group and an intervention group. The intervention group received visual biofeedback cycling training (MOTOmed viva2 system) once per week for 3 months, and a home exercise program. The control group only received the home exercise program. Both groups were evaluated using the GAITRite® Walkway gait assessment system before the intervention, during the first month of the programme, and after the intervention. RESULTS: In the intervention group, the analysis revealed statistically significant differences between Functional Ambulation Profile (FAP) scores before and during the intervention (P=.014), and before and after the intervention (P=.002). A statistically significant improvement was observed in step length in the intervention group between pre- and post-intervention scores (P=.001) and between first-month and post-intervention scores (P=.004). CONCLUSIONS: Visual biofeedback cycling training improved specific gait parameters in the short term and appears to be a therapeutic option for gait retraining in patients with MS.

Optimizing clinical care of patients with metastatic breast cancer: a new oral vinorelbine plus trastuzumab combination.

BACKGROUND: Trastuzumab (T) combined with i.v. vinorelbine (i.v.VNR) is an active regimen for patients with advanced breast cancer (ABC). In order to further improve quality of life of patients undergoing treatment for ABC, a new regimen using oral vinorelbine (oVNR) (d1 + d3) plus q3wks T was tested (ToVNR). PATIENTS AND METHODS: Thirty-nine patients with ABC, human epidermal growth factor receptor 2/neu 3+ or FISH positive received 288 treatment cycles with T 6 mg/kg (loading dose, 8 mg/kg) on d1 and oVNR 55 mg/m(2) on d1 + d3, q3wks until disease progression or unacceptable toxicity. RESULTS: Thirty-seven patients and 286 treatment cycles were evaluated (two patients were lost to follow-up). Treatment was very well tolerated. Two patients had complete response (CR), 14 partial response (PR), 17 stable disease (SD) and four disease progression (PD) (overall response rate: 43%). Clinical benefit rate (CR + PR + SD >24 months) was 73%. Median time to progression was 8.9 months (range 2-27) and median duration of response was 10.9 months (range 2-27). CONCLUSIONS: The ToVNR combination is active and very well tolerated. It favorably compares with the combination of T and weekly i.v. administered VNR, allowing a more convenient once every three weeks hospital admission and leaving patients and care providers free from the unpleasant effect of i.v.VNR.

Brain metastases in patients with advanced breast cancer.

BACKGROUND: The incidence of brain metastases (BM) is apparently rising in patients with advanced breast cancer (ABC). We performed a case control study to define current features of breast cancer related to central nervous system (CNS) metastases. PATIENTS AND METHODS: From March 1999 to May 2006, we identified 72 patients with symptomatic BM of breast cancer. A comparison group was randomly selected assigning to each case two patients with primary breast cancer and no BM, matched for year of diagnosis, age and tumour stage (pT status and nodal status). RESULTS: Cases had a significantly higher rate of negative estrogen receptors (ERs) (60% in cases vs. 29% in controls), negative progesterone receptors (PgRs) (79% vs. 43%), HER2/neu over expression (44% vs. 13%) and immunostaining for Ki-67 > or =20% (84% vs. 55%), with p-value <0.001 for all four parameters in univariate analyses. On multivariate analysis, HER2/neu over expression and Ki-67 -20% were independent predictive factors of brain relapse (Odds Ratio (OR) 2.55, 95% confidence intervals (CI) 1.10-5.94 and OR 2.97, 95% CI 1.01-8.73, respectively). Endocrine unresponsive tumours (both ER and PgR <10%) showed an increased risk of relapse with BM of borderline significance (OR 1.91, 95% CI 0.87-4.12). CONCLUSION: Patients with ER and PgR negative tumours either with or without HER-2/neu over expression should be considered at higher risk of BM.

Treatments for colorectal liver metastases: A new focus on a familiar concept.

A major challenge for the management of advanced-colorectal-cancer is the multidisciplinary approach required for the treatment of liver metastases. Reducing the burden of liver metastases with liver-directed therapy has an important impact on both survival and health-related quality of life. This paper debates the rationale and current liver-directed approaches for colorectal liver metastases based on the evidence of literature and new clinical trials. Surgery is the gold standard, when feasible, and it's the main treatment goal for patients with potentially-resectable disease as a means of prolonging progression-free survival. Better tumor response rates with modern systemic therapy mean that more unresectable patients are now down-staged for radical resection following conversion therapy but for other patients, additional procedures are needed. In multiple unilobar disease, when the projected remnant liver is <30% of the total liver, portal embolization or selective-internal-radiation-therapy (SIRT) can induce hypertrophy of the healthy liver, leading to resectability. In multiple bilobar disease, in situ destruction of non-resectable lesions by minimally invasive techniques may be associated with liver resection to achieve potential curative intent. Other palliative liver-directed approaches, such as SIRT or intra-hepatic chemotherapy (HAI), which are associated with higher response rates, may also have role in down-staging patients for resection. Until recently, such technologies have not been validated in prospective controlled trials. However in the light of new Phase 3 data for SIRT as well as for HAI combined with modern therapies or radiofrequency ablation in the first- and second-line setting, the clinical value of these treatments needs to be re-appraised.

Efectos del entrenamiento en bicicleta con retroalimentación visual sobre la marcha en pacientes con esclerosis múltiple / Effect of visual biofeedback cycling training on gait in patients with multiple sclerosis

INTRODUCCIÓN: Las alteraciones de la marcha están presentes en un alto porcentaje en los pacientes con esclerosis múltiple (EM); aparece desde estadios iniciales pudiendo limitar la realización de las actividades básicas de la vida diaria y afectando a su calidad de vida. El entrenamiento en bicicleta con retroalimentación visual se presenta como una herramienta útil en el tratamiento de estas alteraciones. El objetivo del presente estudio es valorar el efecto a corto plazo del entrenamiento en bicicleta con retroalimentación visual sobre las alteraciones de la marcha en pacientes con EM. MATERIAL Y MÉTODOS: Sesenta y un pacientes con EM con afectación leve-moderada, distribuidos aleatoriamente en un grupo control y un grupo experimental participaron en el estudio. El grupo experimental fue sometido a entrenamiento con bicicleta con biofeedback visual (sistema MOTOmed Viva2) un día en semana durante 3 meses y un programa domiciliario de ejercicios. El grupo control tuvo solo el programa domiciliario de ejercicios. Valoración mediante el sistema de análisis de marcha GAITRite ® Walkway de ambos grupos, pre, al mes y postintervención. RESULTADOS: Resultados estadísticamente significativos en el parámetro FAP del grupo experimental entre el pre y al mes (p = 0,014) y el pre y postintervención (p = 0,002). Mejoró significativamente la diferencia de la longitud de paso del grupo experimental entre el pre y post (p = 0,001) y entre el mes y el postintervención (p = 0,004). CONCLUSIONES: El tratamiento con la bicicleta mejoró a corto plazo determinados parámetros de la marcha, pudiéndose mostrar como opción terapéutica en la reeducación de la marcha en pacientes con EM

INTRODUCTION: Gait alterations are present in a high percentage of patients with multiple sclerosis (MS). They appear from early stages of the disease and can limit patients' capacity to perform basic activities of daily living, affecting their quality of life. Visual biofeedback cycling training appears to be a useful tool in treating these impairments. This study aims to evaluate the short-term effect of visual biofeedback cycling training on gait in patients with MS. MATERIAL AND METHODS: A total of 61 patients with mild to moderate MS were randomly assigned to a control group and an intervention group. The intervention group received visual biofeedback cycling training (MOTOmed viva2 system) once per week for 3 months, and a home exercise program. The control group only received the home exercise program. Both groups were evaluated using the GAITRite ® Walkway gait assessment system before the intervention, during the first month of the programme, and after the intervention. RESULTS: In the intervention group, the analysis revealed statistically significant differences between Functional Ambulation Profile (FAP) scores before and during the intervention (P = .014), and before and after the intervention (P = .002). A statistically significant improvement was observed in step length in the intervention group between pre- and post-intervention scores (P = .001) and between first-month and post-intervention scores (P = .004). CONCLUSIONS: Visual biofeedback cycling training improved specific gait parameters in the short term and appears to be a therapeutic option for gait retraining in patients with MS

Behavioral disorders in Alzheimer disease: a transcultural perspective.

OBJECTIVES: To compare 2 samples of patients with Alzheimer disease (AD), from Italy and the United States, in order to determine transcultural differences in the manifestation of noncognitive symptoms. To analyze the concurrent validity, internal consistency reliability, between-rater reliability, and test-retest reliability of the Neuropsychiatric Inventory Scale (NPI). METHODS: The NPI was given to 50 Italian and 50 US patients with AD. To demonstrate the validity and reliability of the Italian version of the instrument, several different methods of analysis were used. The total score on the NPI and the score of single items in the different stages of the disease were compared in the 2 samples of patients. RESULTS: A high level of internal consistency reliability was confirmed, the between-rater reliability was very high, and the test-retest reliability was significantly correlated. Apathy was the most frequently recorded behavior in the Italian sample. Five of 10 NPI item scores showed a significant relation with the Mini-Mental State Examination scores in both samples. The Italian patients showed an increasing and significantly higher mean NPI total score at all levels of dementia severity when compared with the US patients. The scores on some NPI subscales, such as apathy, aberrant motor behavior, disinhibition, and agitation, were significant higher in Italian patients at different levels of severity covarying with educational level. CONCLUSIONS: These results indicate that NPI is a reliable instrument with which to study transcultural differences in the presentation of neuropsychiatric disturbances in patients with AD. The described similar pattern of behaviors between Italians and US patients with AD suggests a biological origin of the disorders. However, cultural influences must be taken in account when the focus of the study is on psychopathological aspects of dementia.

Release from proactive interference in early Alzheimer's disease.

The study analyses the performance of 22 mild Alzheimer's disease (AD) patients on the Release from Proactive Interference (RPI) paradigm with the aim to investigate the relationship of RPI with frontal function. Twenty-one normal elderly subjects, age and education matched, constituted the control group. Patients with AD were found to recall less words on each trial of the RPI than did the controls. The analysis of Proactive Interference (PI) and Release from PI, in AD patients, by using Anova (trial x group), showed a significant effect of trial and group but not a group by trial interaction. These results indicate a similarity between the performance of AD patients and normal controls on the Release from Proactive Interference paradigm. Despite the similar pattern of performance, AD patients were significantly inferior to normal controls with regard to global performance level. The AD patients' scores on "frontal lobe" tests were correlated with an index of RPI (shift condition index). The only significant result was with the number of categories on the Wisconsin Card Sorting Test, suggesting a weak correlation between RPI and "frontal lobe" function.

The effect of nimesulide on prostanoid formation.

Nimesulide (4-nitro-2-phenoxy-methansulfonanilide) is a weak acidic (pKa = 6.50) nonsteroidal anti-inflammatory drug (NSAID) belonging to a new chemical class, the sulfonanilide derivatives, and does not contain the carboxylic group. It exhibits potent anti-inflammatory, analgesic and antipyretic activities. Although nimesulide is not a cyclo-oxygenase inhibitor in gastric tissues or bovine seminal vesicle microsomes, it inhibits prostaglandin synthesis in zymosan-stimulated murine macrophages in inflammatory exudate. Nimesulide significantly antagonises the immune formation of thromboxane B2 in lung tissue. It neither induces gastrointestinal lesions nor affects renal function in animal models.

Recent contributions to knowledge of the mechanism of action of nimesulide.

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) of the sulfonanilide class. Its anti-inflammatory, analgesic and antipyretic activities have been demonstrated in several widely used animal experimental models and in numerous clinical trials. Nimesulide only weakly inhibits prostaglandin synthesis and appears to exert its effects through various mechanisms. It inhibits the release of oxidants from activated neutrophils and has a scavenging effect on hypochlorous acid without affecting neutrophil function. Nimesulide also decreases histamine release from tissue mast cells and inhibits the production of platelet-activating factor by human basophils. Furthermore, when added in vitro to cultures of human articular chondrocytes, nimesulide inhibits the release of stromelysin and blocks metalloproteinase activity.

Tolerability of nimesulide. Epidemiological data.

This review describes the tolerability profile of nimesulide as documented in a global assessment of the clinical data available to Helsinn for this drug. Data from 151 trials were considered and the relevant case report forms and study reports were used as source information. The analysis was conducted using between-treatment and within-treatment comparisons. The between-treatment comparison included data derived from placebo-controlled trials, while the within-treatment comparison included nimesulide data only. Of 4945 subjects treated with nimesulide, 349 (7.1%) experienced adverse events and 52 (1.1%) withdrew from treatment. The most frequently reported adverse events were those related to the digestive system, body as a whole, skin and nervous system. The incidence and nature of adverse events observed for nimesulide-treated patients were similar to those of the placebo group. Nimesulide was particularly well tolerated by the liver, lungs, kidneys and blood.

Regulation of endothelial cell shape and barrier function by chromogranin A.

We have found that chromogranin A (CgA), a protein released in circulation by neuroendocrine cells and neurons, prevents the vascular leakage induced by tumor necrosis factor (TNF) in a mouse model. Studies of the mechanism of action showed that CgA and its NH(2)-terminal fragments inhibit TNF-induced vascular permeability by preventing endothelial cytoskeleton rearrangements. We propose that neuronal/endocrine secretion of CgA could contribute to the regulation of endothelial barrier function and the protection of vessels against plasma leakage in inflammatory diseases.