Dexamethasone-Sparing Regimens with Oral Netupitant and Palonosetron for the Prevention of Emesis Caused by High-Dose Cisplatin: A Randomized Noninferiority Study

Background: To reduce the overall exposure to dexamethasone (DEX) in patients receiving cisplatin-based chemotherapy, we evaluated the noninferiority of DEX on day 1, with or without low-dose DEX on days 2 and 3, combined with an oral fixed-dose combination of netupitant and palonosetron (NEPA), compared with the guideline-consistent use of 4-day DEX. Patients and Methods: In this open-label, multicenter study, chemotherapy-naïve patients undergoing high-dose cisplatin (≥70 mg/m2), were given NEPA and DEX (12 mg) on day 1 and randomized (1:1:1 ratio) to receive either (a) no further DEX (DEX1), (b) oral DEX (4 mg daily) on days 2–3 (DEX3), or (c) DEX (4 mg twice daily) on days 2–4 (DEX4). The primary efficacy endpoint was complete response (CR: no emesis and no rescue medication) during the 5-day overall phase. The noninferiority margin was set at −15% difference (DEX1 or DEX3 minus DEX4). Secondary efficacy endpoints included complete protection (CP: CR and none or mild nausea). Results: Two-hundred twenty-eight patients, 76 in each arm, were assessable. Noninferiority was met for both DEX-sparing regimens and the reference arm, with overall phase CR rates of 76.3% in each of the DEX1 and DEX3 arms and 75.0% in the DEX4 arm (95% confidence interval, −12.3% to 15% for each comparison). During the overall phase, CP rates were similar between groups. Conclusion: A simplified regimen of NEPA plus single-dose DEX offers comparable chemotherapy-induced nausea and vomiting prevention throughout 5 days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high–emetic-risk setting of cisplatin-based chemotherapy. Implications for Practice: Dexamethasone (DEX) has traditionally played an integral role in the management of chemotherapy-induced emesis. Although generally considered safe, even short-term DEX use is associated with various side effects, and some evidence suggests that concurrent steroids may reduce the efficacy of immunotherapies. This study demonstrates comparable antiemetic control during the 5 days post-chemotherapy with a simplified regimen of netupitant/palonosetron plus single-dose DEX versus the standard 4-day DEX reference treatment in high-dose cisplatin. This represents a clinically relevant achievement as it not only simplifies antiemetic prophylaxis but also offers an opportunity to appropriately use in patients where caution with corticosteroid use is advised

Immunological backbone of uveal melanoma: is there a rationale for immunotherapy?

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease

ESCRITÓRIOS ABERTOS: UM DEBATE NA CONFLUÊNCIA DA ARQUITETURA E DA ERGONOMIA

Este artigo trata dos ambientes de escritórios e suas tipologias, objetivando verificar a melhor representante da conjunção dos interesses organizacionais e dos trabalhadores. Pretende-se clarear os ganhos da agregação de preceitos ergonômicos ao projeto arquitetônico e mostrar que o ambiente de trabalho pode ser utilizado visando desempenhos otimizados. O campo empírico focalizou-se numa análise crítica do modelo de escritório mais utilizado atualmente: o escritório aberto. O estudo de caso considerou dois ambientes de escritórios nesta tipologia, tendo como escopo a arquitetura do lugar de trabalho, que não se demonstrou condizente às suas necessidades ergonômicas. Os dados coletados evidenciam esta desarmonia

Bipolar disorder in late life: clinical characteristics in a sample of older adults admitted for manic episode

BACKGROUND: Although manic episodes in older adults are not rare, little published data exist on late-life manic episodes. Resistance to treatment and concomitant neurological lesions are frequent correlates of elderly mania. The aim of this study was to investigate the prevalence of hospitalizations due to mania in patients older than 64 years through a period of 5 years in an Italian public psychiatric ward. Moreover, we aimed at describing clinical presentation of elderly manic episodes. METHODS: A retrospective chart review was conducted in order to describe clinical presentation of 20 elderly patients hospitalized for manic episode; moreover, we compared age at onset, the presence of family history for mood disorders, psychosis and irritability between the elderly group and a matched group of 20 younger manic inpatients. RESULTS: Seven percent of the whole inpatient elderly people suffered from mania. Half of those patients had a mood disorder age at onset after 50 years and 5 patients were at their first manic episode. Geriatric- and adulthood mania showed similar clinical presentation but younger people had more frequently a mood disorders family history. CONCLUSION: Half of our older manic inpatients consisted of "classic" bipolar patients with an extension of clinical manifestations into later life; the other half of our sample was heterogeneous, even though it was not possible to identify clearly which patients may have had vascular lesions related to the onset of mania

Formación en Cuidados Paliativos: un paso decisivo hacia la calidad del final de la vida

Palliative Care is an answer to the growing need of care for pa- tients suffering from incurable diseases, whose management is often burdened by the inadequacy of the social and family networ- ks, by limited resources and poor training of health workers. Al- though the institutional pathway of this new discipline is on its way, the knowledge of its founding principles is still very limited, both among citizens and, even more surprisingly, among the same operators, who still see Palliative Care as a “consolation and frustration medicine”. On the other hand, this discipline focu- ses on the dignity of men till the end of life, trying to give a global answer to all their needs and those of their families. If the center of the health care response is the human being, then it should be the same patient to be able to identify his needs and thus to enter  into the decision-making process. In order to achieve this level of care relationship, synergistic and aware, and a real sharing of res- ponsibilities, patients must go through a gradual understading of their own disease condition. A trained physician should guide pa- tients through this foundamental journey. In fact, people appro- aching the end of life do indeed need high quality care, which should meet all their inner spheres, but also continuity of care and stable and mature therapeutic relationships. Similarly, every heal- th worker who lives patients’ end of life should have proper tools not to be damaged and not to be overwhelmed by the intensity of these relationships. In this context, a Master in Palliative Care is meant to develop specialized skills and fill the educational gap and it should be the first step towards a deep and claimed cultural change in our country.Los Cuidados Paliativos son una respuesta a la creciente necesi- dad de asistencia para los enfermos afectados por patologías in- curables, cuyo trabajo de atención está frecuentemente agravado por la inadecuación de la red social y familiar, por la escasez de los recursos destinados a ellos y por la carencia formativa de los operadores sanitarios. Si bien el camino institucional de esta nue- va disciplina esté en un buen punto, el conocimiento de sus prin- cipios fundantes es todavía muy limitado tanto por parte de los ciudadanos como, todavía más sorprendentemente, por parte de los mismos operadores, que todavía ven en los Cuidados Paliati- vos una medicina del consuelo y de la frustración. Al contrario, esta disciplina encuentra su propio centro en la dignidad del hom- bre hasta el final de la vida, proponiéndose responder en manera global a todas sus necesidades y a aquellas del núcleo familiar. Si el centro de esta respuesta asistencial es el hombre, entonces es necesario hacer al mismo paciente capaz de identificar sus propias necesidades y entrar así en el proceso decisional de su propio tratamiento. Para llegar a este tipo de relación de trata- miento, sinérgica y consciente, y a una real participación de las responsabilidades, se debe necesariamente pasar a través de una progresiva toma de consciencia de la condición de enfermo. Este camino debe ser guiado in primis por un médico formado en este sentido. Quien se acerca al final de la vida tiene de hecho necesidad de cuidados de alta calidad, que respondan a todas las esferas de la persona implicadas en la enfermedad, de continui- dad en la asistencia y de relaciones terapéuticas estables y ma- duras. Igualmente, también el operador que vive la asistencia al final de la vida debe tener los instrumentos adecuados para no dañarse y dejarse superar por la intensidad de estas relaciones. De este contexto nace la necesidad de un Master de estudios que desarrolle competencias especializadas y colme el vacío for- mativo en modo uniforme como primer paso hacia un profundo y necesario cambio cultural

Predictive value of NLR, TILs (CD4+/CD8+) and PD-L1 expression for prognosis and response to preoperative chemotherapy in gastric cancer

The combination of perioperative chemotherapy plus complete surgical resection is currently accounted as the first-choice strategy in patients with locally advanced Gastric Cancer (LAGC). Nevertheless, the partial response rate makes it necessary to search biological parameters useful to select patients who would benefit most from neoadjuvant chemotherapy (NAD-CT). We performed a retrospective analysis on a cohort of 65 LAGC cases, EBV negative and without MMR defect, submitted to perioperative chemotherapy plus surgical resection. We evaluated the neutrophil-lymphocytes ratio (NLR) in peripheral blood, the TILs density (reported as CD4/CD8 tissue ratio) and PD-L1 expression by immunohistochemistry on bioptic tissues before the treatment. Results were correlated with the biological features, histological response (TRG) and clinical outcome (PFS and OS). We found that NLR, TILs and PD-L1 expression showed a significant correlation with TNM stage, lymphovascular invasion and response to NAD-CT (TRG). Correlating the NLR, TILs and PD-L1 expression with PFS and OS, we found that patients with lower NLR levels (< 2.5 ratio), lower TILs (< 0.2 ratio) and higher PD-L1 level (CPS ≥ 1) had a significantly better PFS and OS than those with higher NLR, higher TILs and lower PD-L1 expression (p < 0.0001). Multivariate and multiple regression analyses confirmed the predictive and prognostic role of all three parameters, especially when all three parameters are combined. Our study demonstrated that pre-treatment NLR, TILs and PD-L1 expression are predictive and prognostic parameters in NAD-CT-treated LAGC suggesting a pivotal role of the systemic and tumor microenvironment immunological profile in the response to chemotherapy

Complete Metabolic Response with Recanalization of Portal Vein Tumor Thrombosis after Sunitinib in a Patient with Advanced Hepatocellular Carcinoma

The prognosis of patients with advanced hepatocellular carcinoma (HCC) is very poor. The outcome of these patients is particularly bleak when the disease is complicated by portal vein tumor thrombosis (PVTT), since the increased portal pressure often causes serious gastrointestinal bleedings. Before the introduction of sorafenib (SOR), a tyrosine kinase inhibitor, no effective treatment was available for patients with advanced disease. SOR is now considered the standard treatment even for patients with tumor thrombosis, although the well-known interference between tyrosine kinase inhibitors and the coagulation pathway calls for caution against their use in this setting. Here, we report the case of a 74-year-old male patient with advanced HCC and PVTT treated with sunitinib (SUN), another multikinase inhibitor. During the third cycle, our patient experienced a life-threatening hematemesis with hemorrhagic shock that required intensive care treatment and SUN discontinuation. However, he completely recovered, and the PET/CT scan performed 1 year after the adverse effect demonstrated no evidence of the tumor together with portal vein recanalization. The short course of SUN causing both tumor response and gastrointestinal bleeding warrants further studies on the effectiveness of SUN in this setting as well as on the duration of treatment with multikinase inhibitors in patients with tumor thrombosis

Charcot-Marie-Tooth type 2CC misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Background and aims: Charcot-Marie-Tooth (CMT) is a heterogeneous group of genetic neuropathies and is typically characterized by distal muscle weakness, sensory loss, pes cavus and areflexia. Herein we describe a case of CMT2CC presenting with proximal muscle weakness and equivocal electrophysiological features, that was misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). Case report: A 30-year-old woman complained of proximal muscle weakness with difficulty climbing stairs. Neurological examination showed weakness in lower limb (LL) muscles, that was marked proximally and mild distally, and absence of deep tendon reflexes in the ankles. Nerve conduction studies (NCS) showed sensory-motor neuropathy with non-uniform NC velocity and a partial conduction block (CBs) in peroneal nerve and tibial nerves. Thus, a diagnosis of CIDP was entertained and the patient underwent ineffective treatment with intravenous immunoglobulins. At electrophysiological revaluation CB in peroneal nerve was undetectable as also distal CMAP had decreased whereas the CBs persisted in tibial nerves. Hypothesizing a hereditary neuropathy, we examined the proband's son, who presented mild weakness of distal and proximal muscles at lower limbs. Neurophysiological investigation showed findings consistent with an intermediate-axonal electrophysiological pattern. A targeted-NGS including 136 CMT genes showed the heterozygous frameshift mutation (c.3057dupG; p.K1020fs*43) in the NEFH gene, coding for the neurofilament heavy chain and causing CMT2CC. Interpretation: Diagnosis of a genetic neuropathy may be challenging when clinical features are atypical and/or electrophysiological features are misleading. The most common misdiagnosis is CIDP. Our report suggests that also CMT2CC patients with proximal muscle weakness and equivocal electrophysiological features might be misdiagnosed as CIDP

Augmentation of Clozapine with Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study

AIM: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated. PATIENTS: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGI-Severity of 59.1+/-12.0 and 5.4+/-0.5, respectively, were treated with clozapine (mean dose 292.9+/-220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 +/- 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection. RESULTS: Total scores at BPRS decreased significantly (from 59.1+/-12.0 to 51.1+/-15.6, p=0.007) after aripirazole augmentation. In particular, the factors "thought disorder" (from 10.4+/-4.4 to 9.0+/-4.5, p=.047) and "anergia" (from 10.0+/-2.7 to 8.0+/-2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well. CONCLUSION: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation