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Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT. Supplementary Information The online version contains supplementary material available at 10.1007/s00520-021-06472-7.

This study investigated the effect of 4-d acute thermal treatments at 18 °C, 26 °C (control) and 34 °C on the nervous system of adult zebrafish (Danio rerio) using a multidisciplinary approach based on behavioural tests and brain proteomic analysis. The behavioural variations induced by thermal treatment were investigated using five different tests, the novel tank diving, light and dark preference, social preference, mirror biting, and Y-Maze tests, which are standard paradigms specifically tailored for zebrafish to assess their anxiety-like behaviour, boldness, social preference, aggressiveness, and explorative behaviour, respectively. Proteomic data revealed that several proteins involved in energy metabolism, messenger RNA translation, protein synthesis, folding and degradation, cytoskeleton organisation and synaptic vesiculation are regulated differently at extreme temperatures. The results showed that anxiety-like behaviours increase in zebrafish at 18 °C compared to those at 26 °C or 34 °C, whereas anxiety-related protein signalling pathways are downregulated. Moreover, treatments at both 18 °C and 34 °C affect the exploratory behaviour that appears not to be modulated by past experiences, suggesting the impairment of fish cognitive abilities. This study is the continuation of our previous work on the effect of 21-d chronic treatment at the same constant temperature level and will enable the comparison of acute and chronic treatment effects on the nervous system function in adult zebrafish.

PURPOSE Unmet needs for advanced-disease cancer patients are fatigue, pain, and emotional support. Little information is available about the feasibility of interventions focused on patient-reported outcome measurement developed according to the Medical Research Council (MRC) Framework in advanced-disease cancer patients. We aimed to pilot a nurse-led complex intervention focused on QoL assessment in advanced-disease cancer patients. METHODS The INFO-QoL study was based on an exploratory, nonequivalent comparison group, pre-test-post-test design. Study sites received either the INFO-QoL intervention or usual care. Adult advanced-disease cancer patients admitted to hospice inpatient units that gave their informed consent were included in the study. Subjects were 187 patients and their families and 19 healthcare professionals. We evaluated feasibility, acceptability, and patients' outcomes using the Integrated Palliative Care Outcome Scale. RESULTS Nineteen healthcare professionals were included. The mean competence score increased significantly over time (p

Background The application of different models of autologous stem-cell transplantation (ASCT) in multiple myeloma has demonstrated the feasibility and safety of outpatient-based programs of care. Although several systematic reviews have evaluated the burden of caregivers, only a few studies have included outpatient ASCT. Patients and Methods The feelings of lack of family support, daily activities, and general health were compared between caregivers of 2 groups of patients with multiple myeloma who underwent inpatient (n = 71) or outpatient (n = 25) ASCT. Results The 3 features did not significantly differ between the 2 study groups at baseline, before, and 3 months after ASCT. Multivariate modeling showed that the baseline values were significantly related to the changes in study outcomes independent of patient and caregiver characteristics. Other correlates were caregivers’ work and patient age for impact on daily activities and disease burden across time for impact on general health (all P Conclusion The outpatient model neither improves nor impairs global caregivers’ burden compared to standard ASCT care. Further research is needed to confirm this observation and to better assess the burden and quality of life of caregivers and their influence on patient outcomes and quality of life.

Proteomic technologies have identified 234 peptidases in plasma but little quantitative information about the proteolytic activity has been uncovered. In this study, the substrate profile of plasma proteases was evaluated using two nano-LC-ESI-MS/MS methods. Multiplex substrate profiling by mass spectrometry (MSP-MS) quantifies plasma protease activity in vitro using a global and unbiased library of synthetic peptide reporter substrates, and shotgun peptidomics quantifies protein degradation products that have been generated in vivo by proteases. The two approaches gave complementary results since they both highlight key peptidase activities in plasma including amino- and carboxypeptidases with different substrate specificity profiles. These assays provide a significant advantage over traditional approaches, such as fluorogenic peptide reporter substrates, because they can detect active plasma proteases in a global and unbiased manner, in comparison to detecting select proteases using specific reporter substrates. We discovered that plasma proteins are cleaved by endoproteases and these peptide products are subsequently degraded by amino- and carboxypeptidases. The exopeptidases are more active and stable in plasma and therefore were found to be the most active proteases in the in vitro assay. The protocols presented here set the groundwork for studies to evaluate changes in plasma proteolytic activity in shock.

Bochdaleck hernia (BH) is a congenital diaphragmatic hernia that presents after birth with respiratory symptoms and needs surgical treatment in the neonatal period. However, there are some rare cases of adult presentation, which require surgery to avoid complications. BHs can be treated through several approaches, including laparoscopy. Laparoscopic treatment of a giant BH was successfully attempted on a woman affected by multiple myeloma, with severe dyspnoea and dysphagia. Preoperative work-up included chest X ray, CT-scan and MRI. The whole stomach, duodenum, the small bowel, the right and transverse colon, most descending colon and the pancreas were herniated into the thorax. The herniated viscera were totally reduced into the abdominal cavity and the large defect of the left diaphragm repaired with a biosynthetic web scaffold especially designed for diaphragmatic reconstruction. Finally, to avoid a compartment syndrome in an abdomen with not enough room for the reduced viscera, an extended right colectomy with extracorporeal anastomosis was carried out through a mini-laparotomy. At seven-month follow-up, the patient is symptomless and control CT scan showed no hernia recurrence. Laparoscopic repair of large symptomatic adult BHs can be performed successfully with significant clinical improvement, even in difficult cases and fragile patients.

The histones which pack new DNA during the S phase of animal cells are made from mRNAs that are cleaved at their 3' end but not polyadenylated. Some of the factors used in this reaction are unique to it while others are shared with the polyadenylation process that generates all other mRNAs. Recent work has begun to shed light on how the cell manages the assignment of these common components to the two 3' processing systems, and how it achieves their cell cycle-regulation and recruitment to the histone pre-mRNA. Moreover, recent and older findings reveal multiple connections between the nuclear organization of histone genes, their transcription and 3' end processing as well as the control of cell proliferation.

PI3K is one of the most frequently mutated genes in cancers and has been the target of numerous anticancer therapies. With the additional development of therapeutics that mobilize the immune system, such as Abs with effector functions, bispecific Abs, and checkpoint inhibitors, many small molecule inhibitors that target PI3K are being combined with these immunomodulatory treatments. However, the PI3K pathway is also essential for lymphocyte function, and the presence of the PI3K inhibitor may render the immunomodulatory therapeutic ineffective in these combinatorial treatments. Therefore, therapeutics with enhanced activity, such as afucosylated Abs, which promote signaling and function, may be ideal in these types of treatments to offset the negative effect of PI3K inhibitors on immune cell function. Indeed, we show that afucosylated Abs can counterbalance these inhibitory effects on FcγRIIIa-driven signaling in human NK cells to produce signals similar to cells treated only with fucosylated Ab. Furthermore, NK cell activation, degranulation, chemokine/cytokine production, and Ab-dependent cellular cytotoxicity were similar between inhibitor-treated, afucosylated Ab–stimulated NK cells and cells activated only with its fucosylated counterpart. To our knowledge, these studies also identified a previously undefined role for phospho-S6 in human NK cells. In this study, a kinetic delay in PI3K-driven phosphorylation of S6 was observed to control transcription of the temporally regulated production of IFN-γ and TNF-α but not MIP-1α, MIP-1β, and RANTES. Together, these studies demonstrate the importance of the PI3K pathway for S6 phosphorylation in human NK cells and the need to combine PI3K inhibitors with therapeutic molecules that enhance immunomodulatory function for anticancer therapies.

Laparoscopic sleeve gastrectomy has become a popular stand-alone procedure among bariatric surgeons. Recently, Natural Orifice Specimen Extraction laparoscopic surgery has been introduced to avoid minilaparotomy, possibly reducing postoperative pain, hospital stay, and improving QoL and cosmetics. Operative steps and preliminary results of NOSE sleeve gastrectomy are described and reported.Five patients underwent NOSE LSG from November 2014 to March 2015. Selection criteria were as follows: age60 years, ASA score ≤III, BMI50. Operative steps are the same of standard LSG, but the stomach transection that starts higher on the greater curvature. A 2–3 cm width opening is created on the exceeding antrum and the resected stomach sutured to the calibration probe tip, which is pull back allowing transoral specimen extraction. The exceeding antrum is stapler-trimmed, allowing breach closure and completion of tubulization.Mean age was 41.6 years (median 43), average weight was 123.6 Kg (median 114), mean BMI 43.6 Kg/m2 (median 44). Mean operation time was 72 min (median 75). Mean and median postoperative stay were 4.6 and 5. No intraoperative nor postoperative complications occurred. Postoperative day 1 mean and median VAS pain score at were 1.4 and 1, respectively. Follow-up ranged 1–5 months (mean and median 3), average weight loss was 19.8 Kg (median 19), and excess weight loss 36.2 % (median 32 %).NOSE LSG potential advantages are as follows: improved cosmetics, decreased postoperative pain, possible incisional hernia rate reduction. No objective data are available to confirm these theoretical benefits; larger observational studies and RCTs are mandatory before clinical validation.

First described in 1982, TME overcomes most of the concerns regarding adequate local control after anterior rectal resection. TME requires close sharp dissection along the so-called Heald's plane down to the levators, with distal dissection often cumbersome. In recent years, Transanal TME was introduced with the aim to improve distal rectal dissection and quality of mesorectal excision.A prospective, non-randomized study, started in 2013, is currently ongoing in two Italian Centers. Study objectives were assessing the safety of TaTME and TME quality. TaTME technique and technologies as performed in these centers and cumulative results at ≤30 postoperative days of the first 102 patients are reported.Early postoperative morbidity and mortality rates were 33.3% (34 pts, 16 Clavien-Dindo I + II and 18 Clavien-Dindo III + IV + V), and 1.96% (two deaths), respectively. The quality of mesorectal excision according to Quirke was: complete in 97.1% and nearly complete in 2.9% of the cases.The results confirm the effectiveness of TaTME, especially regarding the quality of the mesorectal dissection. Open questions regarding standardization, anatomical landmarks, indications, morbidity (with special regard to local infection and sepsis), learning curve and oncological outcomes require further answers from larger studies and RCTs before definitive validation of this procedure. .

Aim Emergency surgery is associated with higher mortality rates, especially in elderly patients presenting with emergent colorectal disease. The aim of this study was to determine the outcomes in elderly patients following emergency colorectal resection, with particular focus on octogenarians who presented a sixfold higher mortality rate with respect to other patients. Method This study examined 355 patients who underwent surgery at an Emergency Department for complications of colorectal disease between January 2007 and December 2009. Morbidity and mortality were analyzed on the basis of patients’ characteristics and presentation. Univariate and logistic regression analyses were performed on morbidity and mortality risk factors. Results Two-hundred and fifteen patients of > 65 years of age were included, 93 of whom were ≥ 80 years of age. The global mortality rate was 16%. In patients ≥ 80 years of age the mortality rate was 30%. The difference in mortality rate between patients

Background: Pneumomediastinum creation, in blunt chest trauma, results from Mackin effect in more than 95% of cases. Objectives: In this article we report two cases of blunt chest trauma, underlining the relationship between Macklin effect, pneumomediastinum and pneumoperitoneum, and analysing conservative and invasive treatment. Case reports: We report two cases of blunt chest trauma with Pneumomediastinum creation and no evidence of airway lesions. The first patient presented with malignant pneumomediastinum, created by Macklin effect, and pneumoperitoneum with intra-abdominal hypertension. He underwent invasive treatment. The second case shows how Macklin effect can be self-limiting. This patient underwent conservative treatment. Conclusions: In any case of post-traumatic pneumomediastinum, the Macklin effect should be suspected. Clinical observation is the treatment of choice since Macklin effect is self-limiting. There are some life-threatening event, like malignant pneumomediastinum and intra-abdominal hypertension that must be relieved and treated immediately.

Laparoscopic colectomy (LC) is slowly becoming the standard of care for elective resections. The use of LC in the emergency setting is relatively unstudied. Authors describe their experience with a series of 34 emergent and urgent LC cases for a variety of benign and neoplastic colorectal diseases, admitted from 2007 to 2009 at Emergency Department of a tertiary level hospital, comparing laparoscopic group with matched control open group. Twenty-one LC was performed for benign complicated disease, 12 for malignant disease and 1 for iatrogenic perforation during colonoscopy. Two cases were converted to open procedure (5.8%), the average operative time was 188 minutes (SD 61.84). The average postoperative length of hospital stay was 6.57 days (SD 1.75), with no postoperative mortality and no major morbidity. Results of laparoscopic group compared with 61 patients treated with open colorectal procedure confirm the advantages of laparoscopic approach similar to those established in elective colorectal surgery. With increasing experience, LC would be a feasible and an effective option in nonelective situations lowering complication rate and length of hospital stay.

Mitochondrial dysfunction has been implicated in the pathogenesis of a number of neurodegenerative disorders including Parkinson, Alzheimer, and Amyotrophic Lateral Sclerosis (ALS). In addition, aberrant mRNA splicing has been documented in neurodegeneration. To characterize the cellular response to mitochondrial perturbations at the level of gene expression and alternative pre-mRNA splicing we used splicing-sensitive microarrays to profile human neuroblastoma SH-SY5Y cells treated with paraquat, a neurotoxic herbicide that induces the formation of reactive oxygen species and causes mitochondrial damage in animal models, and SH-SY5Y cells stably expressing the mutant G93A-SOD1 protein, one of the genetic causes of ALS. In both models we identified a common set of genes whose expression and alternative splicing are deregulated. Pathway analysis of the deregulated genes revealed enrichment in genes involved in neuritogenesis, axon growth and guidance, and synaptogenesis. Alterations in transcription and pre-mRNA splicing of candidate genes were confirmed experimentally in the cell line models as well as in brain and spinal cord of transgenic mice carrying the G93A-SOD1 mutation. Our findings expand the realm of the pathways implicated in neurodegeneration and suggest that alterations of axonal function may descend directly from mitochondrial damage. © 2011 Wiley-Liss, Inc.