Frontline treatment for transplant-eligible multiple myeloma: A 6474 patients network meta-analysis.

Autologous transplantation continues to be the cornerstone of younger and fit multiple myeloma patients. It is known that frontline induction therapy before transplantation can influence post-transplant results. Therefore, best frontline treatment for transplant-eligible patients should be based on best available evidence to guide therapy. Furthermore, until now due to data scarcity, it was not possible to thoroughly compare lenalidomide to other regimens in this setting. We performed a systematic review and network (mixed treatment comparison) meta-analysis of 21 clinical trial publications, enrolling 6474 patients and comparing 11 different treatment frontline setting regimens regarding survival, response, and safety outcomes. OS analysis showed superiority of CRD (cyclophosphamide-lenalidomide-dexamethasone) over TD-based (thalidomide-dexamethasone, HR = 0.76,0.62-0.90), VAD-based (HR = 0.71,0.52-0.90), and Z-Dex (idarubicin-dexamethasone, HR = 0.37,0.17-0.76) regimens. Concerning PFS, VTD (bortezomib-thalidomide-dexametasone) showed superior results when compared with TD-based (HR = 0.66,0.51-0.84), VAD-based (HR = 0.61,0.46-0.82), Z-Dex (HR = 0.42,0.22-0.78), and high dose dexamethasone (Dex, HR = 0.62,0.41-0.90) regimens. Bortezomib/thalidomide regimens were not superior to lenalidomide, considering these outcomes. Also, concerning complete and overall response, VTD ranked first among other regimens, showing clear superiority over thalidomide-only containing protocols. Safety outcome evaluated infectious, cardiac, gastrointestinal, neurological, thrombotic, and hematological grade 3 to 4 adverse events. Risk of thrombotic events was higher with TAD (thalidomide-doxorubicin-dexamethasone), neurological with PAD (bortezomib-doxorubicin-dexamethasone), infectious with Dex, hematological with Z-Dex, gastrointestinal with VTD, and cardiac with PAD regimens. Our study endorses current recommendations on combined immunomodulatory drugs and proteasome inhibitors frontline regimens (in triplets) in transplant-eligible multiple myeloma patients, but also formally demonstrates the favorable performance of lenalidomide in overall and progression-free survival, when compared with bortezomib/thalidomide protocols.

Clinical differences between melancholic and nonmelancholic depression as defined by the CORE system.

BACKGROUND: The definition and delineation of melancholia have remained elusive for an extended period. A longstanding signal of psychomotor disturbance has been operationalized via the observer-rated CORE measure and with CORE-assigned melancholic and nonmelancholic compared in several Australian studies. Replication studies in other regions have not previously been reported. This study compares Brazilian patients with melancholic and nonmelancholic depression according to the CORE measure of psychomotor disturbance in terms of clinical characteristics, suicide ideation, stressful life events, quality of life, parental care, and personality styles. METHODS: A total of 181 patients with unipolar major depression attending a tertiary care outpatient service in Brazil were evaluated in relation to melancholic status and study variables. RESULTS: The CORE-assigned melancholic patients presented higher symptom severity, greater prevalence of suicide ideation, and Axis I comorbidities than nonmelancholics. Scores of dysfunctional personality styles and dysfunctional parental care measures were also higher among melancholics. Quality-of-life scores were low in both groups. LIMITATIONS: The absence of a criterion standard for the diagnosis of melancholia and the use of medication can be potential limitations of the study. CONCLUSION: Differences suggest that CORE-assigned melancholia defines a distinct group of patients and probably a disorder distinct from nonmelancholic depression not only in quantitative but also in qualitative aspects.

Prevalence of psychotic symptoms in those with melancholic and nonmelancholic depression.

The best classification of depressive disorders is still to be established. A melancholic subtype has a lengthy history, and recent research demonstrates its relevance. This study compares the prevalence of psychotic symptoms in nonmelancholic and melancholic depression and assesses whether there is a dimensional pattern in the severity of symptoms among the subtypes. Patients with unipolar depression were assessed for melancholic status, psychotic symptoms, and severity of depression. The diagnosis of melancholia was made by both Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), criteria and CORE measure. The DSM criteria assigned a much higher percentage of patients as melancholics (67.4%) than did the CORE (24.9%). Prevalence of psychosis was distinctly higher in the melancholics. Symptoms severity was higher among the melancholics when compared with the nonmelancholics. The presence of psychotic symptoms was not associated with an increase in the intensity of depressive symptoms. Psychotic symptoms are more frequently associated with the melancholic subtype of depression. This suggests clinical contiguity between the melancholic and psychotic subtypes and the clinical relevance of identifying melancholia.

Upfront treatment for newly diagnosed transplant-ineligible multiple myeloma patients: A systematic review and network meta-analysis of 14,533 patients over 29 randomized clinical trials.

Choice of treatment for newly diagnosed transplant-ineligible multiple myeloma poses a difficult task due to an ever-increasing plethora of different regimens. Attempting to clarify this subject, we performed a systematic review and Bayesian network meta-analysis of 29 randomized clinical trials, enrolling 14,533 patients, and comparing 25 different treatment regimens regarding overall survival(OS), progression-free survival(PFS), complete response(CR), overall response rate(ORR) and toxicity. Head-to-head comparisons for all regimens and ranking of best treatments are reported. OS analysis showed superiority of lenalidomide(R) and bortezomib(V) containing regimens over thalidomide(T) protocols (e.g. Rd/CTD-HR:0.7;95%CrI:0.53-0.93, VMP/TD-HR:95%0.45;CrI:0.29-0.69). Concerning PFS, daratumumab(D) plus V (Dara-VMP) showed superior results over R (e.g. Dara-VMP/MPR-HR:0.52;95%CrI:0.34-0.77), V plus T (Dara-VMP/VTd-HR:0.56;95%CrI:0.37-0.65) and T (Dara-VMP/CTD-HR:0.34;95%CrI:0.23-0.49) containing regimens. Also, VRd and VMPT-VT performed well over other regimens. Dara-VMP showed superior response rates over R (ORR Dara-VMP/MPR-RR:6.27;95%CrI:2.18-18.95, CR Dara-VMP/MPR-RR:1.53;95%CrI:1.21-1.96) and T (ORR Dara-VMP/MPT-T-RR:4.05;95%CrI:1.19-13.26, CR Dara-VMP/MPT-T-RR:1.42;95%CrI:1.09-1.85; ORR Dara-VMP/CTD-RR:2.72;95%CrI:1.2-6.31, CR Dara-VMP/CTD-RR:1.2;95%CrI:1.05-1.36) including a higher rate of complete remission even when compared to VRd (RR:1.29;95%CrI:1.01-1.66). A higher rate of grade 3-4 adverse events was found for RD and CPR (thrombotic); VTd, VTP and VMPT-VT (neurological); RD and VAD (infectious); MPR-R and VAD (hematological); Vd and VTd (gastrointestinal); VAD, VMPCc and RD (cardiovascular). These results confirm obsolescence of classical regimens (such as VAD and MP) while pointing out benefits in efficacy resulting from incorporation of quadruplets and triplets combining new agents (Dara-VMP, VRd and VMPT-VT) and supports current rational of treatment until progression or prohibitive toxicity, especially when including lenalidomide. Based on this data, we would recommended incorporation of strategies combining novel agents (monoclonal antibodies, immunomodulatory imide drugs and proteasome inhibitors) in triplets or quadruplets and/or those comprising long term use of lenalidomide as standard frontline treatments. Moreover, this study settles daratumumab's place as an attractive alternative for upfront treatment.

Pyogenic liver abscess in children: two cases report and literature review

Description of two cases of pyogenic liver abscess. The first case: a 3-years-old immunocompetent girl with fever, abdominal pain, vomiting, and diarrhea. Abdominal ultrasound: multiloculated heterogeneous collection in the right hepatic lobe (figure 1A). The second case, a 1-year-old girl with congenital neutropenia, showed fever,malaise, anorexia, sweating and pallor. Abdominal computed tomography showed hypodense lesion with heterogeneous impregnation by contrast in the left hepatic lobe (figure 1B). Different clinical presentations, images and treatment are of special interest in pediatrics and are reviewed in this text.