On the Identification of the Causal Effects of Audit Activity under Measurement and Selection Biases

We propose a causal analysis based on a linear Structural Equation Model (SEM) of the effect of audits on the compliance level of tax payers. Generally, when the audit rule is not based on randomization and we also have unobserved variables, it is very likely to have confounding and the causal effect estimate can be biased, if not detected by inspection of the graphical model related to the SEM and removed. In addition, both measurement bias and selection bias arise naturally in real situation of observed data, thus increasing the complexity of the problem to be solved. In this case, the classical causal effect identification techniques (backdoor, frontdoor and instrumental variable) cannot be directly applied. To solve the causal effect identification problem in such a context, we extend the effect restoration method for the measurement bias, according to the selection recoverability condition. The proposed method, combining the two techniques, can be used to obtain an estimate of the causal effect closer to the real one, compared to the previous estimation approach adopted in this field. Moreover, the methodology can be applied also in other contexts, on problems sharing the same causal structure, or having an equivalent one

Induction chemotherapy with paclitaxel and cisplatin to concurrent radiotherapy and weekly paclitaxel in the treatment of loco-regionally advanced, stage IV (M0), head and neck squamous cell carcinoma. Mature results of a prospective study

<p>Abstract</p> <p>Background</p> <p>to evaluate activity and toxicity of a sequential treatment in advanced, non metastatic, mostly unresectable, head and neck squamous cell carcinoma.</p> <p>Methods</p> <p>Patients with loco-regionally advanced or unresectable, head and neck cancer, were prospectively treated with 3 courses of induction chemotherapy followed by concurrent chemoradiation. Induction chemotherapy consisted of paclitaxel 175 mg/m2 day 1 and cisplatin 75 mg/m2 day 2, given every 3 weeks, to a total of three courses. Curative radiotherapy started 4 weeks after the last cycle of chemotherapy with the goal of delivering a total dose ≥ 66 Gy. During RT weekly paclitaxel (40 mg/m2) was administered.</p> <p>Results</p> <p>The trial accrued 43 patients from January 1999 to December 2002. All patients received 3 courses of induction chemotherapy and the planned dose of radiotherapy. Thirty-eight patients were able to tolerate weekly paclitaxel during irradiation at least for 4 courses. After induction therapy there were 32 overall responses, 74.4% (23 partial and 9 complete); at completion of concomitant treatment overall responses were 42, 97.7% (20 partial and 22 complete). Median time to treatment failure was 20 months and the disease progression rate at 3 and 5 years was 33% and 23%, respectively. The median overall survival time was 24 months and 3 and 5 years overall survival rates were 37% and 26%, respectively. The major toxicity was mucositis.</p> <p>Conclusions</p> <p>This combined treatment was found to be feasible and active in advanced or unresectable, head and neck squamous cell carcinoma patients. Long-term results observed in this trial encourage to consider this approach in further investigation using newer radiation delivering technique and new molecularly agents.</p

Emerging Targeted Therapies for Castration-Resistant Prostate Cancer

Until recently, few therapeutic options were available for patients with castration-resistant prostate cancer (CRPC). Since 2010, four new molecules with a demonstrated benefit (sipuleucel-T, cabazitaxel, abiraterone, and denosumab) have been approved in this setting, and to-date several other agents are under investigation in clinical trials. The purpose of this review is to present an update of targeted therapies for CRPC. Presented data are obtained from literature and congress reports updated until December 2011. Targeted therapies in advanced phases of clinical development include novel androgen signaling inhibitors, inhibitors of alternative signaling pathways, anti-angiogenic agents, inhibitors that target the bone microenvironment, and immunotherapeutic agents. Radium-223 and MDV3100 demonstrated a survival advantage in phase III trials and the road for their introduction in clinical practice is rapidly ongoing. Results are also awaited for phase III studies currently underway or planned with new drugs given as monotherapy (TAK-700, cabozantinib, tasquinimod, PROSTVAC-VF, ipilimumab) or in combination with docetaxel (custirsen, aflibercept, dasatinib, zibotentan). The optimal timing, combination, and sequencing of emerging therapies remain unknown and require further investigation. Additionally, the identification of novel markers of response and resistance to these therapies may better individualize treatment for patients with CRPC

Bilateral Corneal Perforation in a Patient with Chronic Ocular Graft-Versus-Host Disease: A Case Report and Literature Review

Graft-versus-host disease (GVHD) is a serious complication that may occur in patients receiving allogeneic hematopoietic stem cell transplant (HSCT). GVHD occurs because of the immunological reaction between the donor’s T cells and the recipient’s antigens; GVHD may develop in different tissues, including the eye. Corneal perforation is an uncommon but vision-threatening manifestation of GVHD. We reported the case of a 65-year-old male patient who developed corneal perforation sequentially in both eyes 3 years after receiving HSCT. Conservative treatment with topical steroids and lubricants, bandage contact lens, and lacrimal punctal occlusion surgery resulted in the successful resolution of the corneal perforation with satisfactory visual recovery in the right eye. Therefore, corneal perforation can occur as the presenting manifestation of ocular GVHD. Regular ophthalmological examinations are recommended after HSCT to enable the early diagnosis of ocular GVHD and prompt treatment initiation

Challenges and perspectives in the multidisciplinary management of well-differentiated lung neuroendocrine tumours: a case report

Neuroendocrine tumours of the lung represent a distinct subgroup of primary lung neoplasms, characterized by particular morphologic, ultrastructural, immunohistochemical and molecular peculiarities and different biological behavior. A detailed pathological diagnosis including immunohistochemistry, Ki-67, mitotic rate and necrosis status can be helpful to identify the different subtypes. The optimal management of advanced well-differentiated lung neuroendocrine tumors is still debated and can be very challenging for the clinician. Currently, no established therapeutic algorithm exists for patients with unresectable or metastatic typical carcinoids and atypical carcinoids. To highlight the importance of a multidisciplinary management we report the case of a patient affected by unresectable lung neuroendocrine tumors, who has benefited from integration strategy, resulting in complete surgical excision of the tumour

Challenges with anti-PD1 agents in brain metastases management of NSCLC patients: a case report

Immunotherapy is dramatically changing the therapeutic landscape of advanced Non Small Cell Lung Cancer (NSCLC), with unprecedented results compared with chemotherapy. However, this novel treatment approach poses several novel challenges, including optimal treatment duration, coexistence with other conventional therapies (radiotherapy, targeted therapies, and chemotherapy), and activity in special populations, including patients with brain metastases (BMs). Traditionally, central nervous system (CNS) has been considered an immune-privileged organ, although recent evidences suggest a potential role of the immune system as exploitable target for cancer immunotherapy. Here we present a case of a non-squamous NSCLC patient with a rapid and long-lasting response to the anti-PD1 agent Nivolumab with a remarkable activity in the CNS, without previous brain irradiation

The Mayo ATTR‐CM score versus other diagnostic scores and cardiac biomarkers in patients with suspected cardiac amyloidosis

Aims: Several scores were developed to help the diagnosis of cardiac amyloidosis (CA). The most recent one, being the Mayo transthyretin amyloidosis cardiomyopathy (ATTR-CM) score, was not externally validated. We compared the diagnostic performance of the ATTR-CM score with previous tools (increased wall thickness [IWT] score, AMYLoidosis Index [AMYLI] score, and cardiac biomarkers) in a cohort of patients evaluated for a suspicion of CA. Methods and results: We analysed 362 consecutive patients referred to a third-level centre for suspected CA. Overall, 132 (36%) had transthyretin CA (ATTR-CA), and 91 (25%) immunoglobulin light chain CA (AL-CA); CA was excluded in 139 (38%). ATTR-CM score had a good diagnostic performance to distinguish ATTR-CA from AL-CA or no CA, with an area under the curve (AUC) of 0.795 (95% confidence interval [CI] 0.747-0.842, p &lt; 0.001), and ATTR-CA from no CA (AUC 0.822, 95% CI 0.774-0.871, p &lt; 0.001). Results were consistent in both patients with preserved (AUC 0.787, 95% CI 0.726-0.848, p &lt; 0.001), and reduced or mildly reduced ejection fraction (AUC 0.790, 95% CI 0.709-0.871, p &lt; 0.001). The ATTR-CM score showed a better discrimination compared to IWT and AMYLI score to distinguish ATTR-CA from AL-CA or no CA (p = 0.002), but not to distinguish ATTR-CA from no CA (p = 0.270). Diagnostic accuracy was significantly higher for the ATTR-CM score as compared to the rule-in cut-off of high-sensitivity troponin T. Conclusion: The Mayo ATTR-CM score has a good performance in identifying patients with ATTR-CA, with also better discrimination power when compared to other scores and biomarkers

Vincenzo Consolo: punto de unión entre Sicilia y España. Los treinta años de Il sorriso dell'ignoto marinaio

Con ocasión del trigésimo aniversario de la publicación de Il sorriso dell’ignoto marinaio, hemos organizado las Jornadas Internacionales Vincenzo Consolo: punto de unión entre Sicilia y España. Los treinta años de Il sorriso dell’ignoto marinaio, que se celebraron en la Universitat de València los días 23 y 24 de octubre de 2006 y cuyas Actas ofrecemos en el presente volumen monográfico. De esta manera, cerramos el ciclo de dos años dedicado a la obra de Vincenzo Consolo, ciclo que iniciamos el año anterior con unas primeras Jornadas Internacionales, Lunaria vent’anni dopo, que también organizamos en la Universitat de València los días 24 y 25 de octubre de 2005, al cumplirse el vigésimo aniversario de su obra Lunaria