Second cancers in MPN: Survival analysis from an international study

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.     

Multimodality imaging in COVID-19 patients: A key role from diagnosis to prognosis

The integrated clinical, laboratory and ultrasound approach is essential for the diagnosis, evaluation and monitoring of the patient's therapy in coronavirus disease 2019 pneumonia. The ideal imaging approach in this context is not yet well defined. Chest X-ray is characterized by low sensitivity in identifying earlier lung changes. The "bedside" pulmonary ultrasound has an undeniable series of advantages in the patient at high infectious risk and can provide incremental data in the respiratory intensive care for the serial control of the individual patient as well as for the home delivery of the stabilized subjects. Pulmonary computed tomography shows high sensitivity but should not be routinely performed in all patients, because in the first 48 h it can be absolutely negative and in the late phase the imaging findings may not change the therapeutic approach. Echocardiography should be limited to patients with hemodynamic instability to assess ventricular function and pulmonary pressures.     

Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients

Journal of Thrombosis and Thrombolysis - A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients. In...     

A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.     

Management of rectosigmoid obstruction due to severe bowel endometriosis

Bowel obstruction is a rare complication of intestinal endometriosis. The aim of this work was to evaluate outcomes after colorectal resection for bowel obstruction due to endometriosis. Of 720 patients who underwent colorectal resection for bowel endometriosis, 12 (1.7 %) presented with bowel obstruction. Preoperative work-up, management, perioperative and long-term outcomes were analyzed. All lesions were localized in the rectosigmoid tract. All patients underwent colorectal resection, which was carried out laparoscopically in 4 (33 %). Rate of low or ultra-low colorectal anastomoses was 83 %. Four patients (33 %) required blood transfusions. Two patients developed rectovaginal fistulas. After a median follow-up of 38 months, there were no cases of disease recurrence and dyschezia improved in 75 % of patients. Bowel endometriosis should be considered in the differential diagnosis of young women with bowel obstruction. Despite challenging operations, colorectal resections are associated with good outcomes.     

Depressive symptoms among adolescents and older adults in Mexico City

Purpose

Determine the structure of depressive symptoms among adolescents and older adults through the person-centered approach of latent class analysis (LCA).

Methods

The study is based on data from two independent samples collected in Mexico City (2,444 adolescents and 2,223 older adults) which included the revised version of the CES-D. The presence or absence of depressed mood (dysphoria), diminished pleasure (anhedonia), drastic change in weight, sleep problems, thinking and concentration difficulties, excessive or inappropriate guilt, fatigue, psychomotor agitation/retardation, and suicide ideation were used in LCA to determine the structure of depressive symptoms for adolescents and older adults.

Results

Adolescents reported higher excessive or inappropriate guilt compared to older adults, while older adults had higher proportions of anhedonia, sleep problems, fatigue, and psychomotor agitation/retardation. Similar proportions were found in other symptoms. The LCA analysis showed the best fit with four latent classes (LC): LC 1, “symptoms suggestive of major depressive episode (MDE)” with prevalence of 5.9 % (n = 144) and 10.3 % (n = 230) among adolescents and older adults, respectively; LC 2, “probable MDE symptoms” 18.2 % (n = 446) and 23.0 % (n = 512); LC 3, “possible MDE” 27.7 % (n = 676) and 21.8 % (n = 485); LC 4, “without significant depressive symptoms” 48.2 % (n = 1,178) and 44.8 % (n = 996). The differences in item thresholds between the two groups (adolescents vs. older adults) were statistically significant (Wald test = 255.684, df = 1, p < 0.001).

Conclusions

This study documented important similarities and differences in the structure of depressive symptoms between adolescents and older adults that merit acknowledgment, further study, and consideration of their potential clinical and public health implications.     

Cell types and coincident synapses in the ellipsoid body of Drosophila

Cellular ultrastructures for signal integration are unknown in any nervous system. The ellipsoid body (EB) of the Drosophila brain is thought to control locomotion upon integration of various modalities of sensory signals with the animal internal status. However, the expected excitatory and inhibitory input convergence that virtually all brain centres exhibit is not yet described in the EB. Based on the EB expression domains of genetic constructs from the choline acetyl transferase (Cha), glutamic acid decarboxylase (GAD) and tyrosine hydroxylase (TH) genes, we identified a new set of neurons with the characteristic ring‐shaped morphology (R neurons) which are presumably cholinergic, in addition to the existing GABA‐expressing neurons. The R1 morphological subtype is represented in the Cha‐ and TH‐expressing classes. In addition, using transmission electron microscopy, we identified a novel type of synapse in the EB, which exhibits the precise array of two independent active zones over the same postsynaptic dendritic domain, that we named ‘agora’. This array is compatible with a coincidence detector role, and represents ~8% of all EB synapses in Drosophila. Presumably excitatory R neurons contribute to coincident synapses. Functional silencing of EB neurons by driving genetically tetanus toxin expression either reduces walking speed or alters movement orientation depending on the targeted R neuron subset, thus revealing functional specialisations in the EB for locomotion control.     

Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit–hyperactivity disorder (ADHD)

It has been proposed that the neurotrophin brain-derived neurotrophic factor (BDNF) may be involved in attention deficit–hyperactivity disorder (ADHD) etiopathogenesis. Alterations in BDNF serum levels have been observed in childhood/adulthood neurodevelopmental pathologies, but no evidence is available for BDNF serum concentrations in ADHD. The study includes 45 drug-naïve ADHD children and 45 age–sex matched healthy subjects. Concentration of serum BDNF was determined by the ELISA method. BDNF serum levels in patients with ADHD were not different from those of controls (mean ± SD; ADHD: 39.33 ± 10.41 ng/ml; controls: 38.82 ± 8.29 ng/ml, t = ?0.26, p = 0.80). Our findings indicate no alteration of serum BDNF levels in untreated patients with ADHD. A further stratification for cognitive, neuropsychological and psychopathological assessment in a larger sample could be useful to clarify the role of BDNF in the endophenotype characterization of ADHD.     

Intracystic Gadolinium‐Enhanced MRI in the Evaluation of Residual Giant‐Cystic Craniopharyngiomas in Children: Report of Four Cases

Residual giant‐cystic craniopharyngiomas are amenable to intracavitary bleomycin treatment. Radiologic identification of potential cyst leaks is of paramount for treatment decisions. This report describes our experience in the use of intracystic Gadolinium (Gd)‐enhanced MR imaging to determine potential communications between the tumoral cysts and other intra‐axial spaces in 4 pediatric patients with residual giant‐cystic craniopharyngiomas in whom intracavitary bleomycin treatment was planned after the injection of .1‐.2 mL of gadopentetate dimeglumine (Gd‐DTPA). In three cases no leaks were found. In one case, whose previous water‐soluble iodinated contrast‐enhanced CT cystography was negative for leaks, intracystic Gd‐enhanced MR showed intraventricular Gd enhancement. We conclude that MR imaging after intracystic administration of Gd‐based contrast paramagnetic agents is useful in the detection of potential leaks in cases of giant residual craniopharyngiomas.