Donor compatibility and performance status affect outcome of allogeneic haematopoietic stem cell transplant in patients with relapsed or refractory acute myeloid leukaemia

We retrospectively analysed 78 patients with relapsed (n?=?38), primary refractory (n?=?34) or untreated (n?=?6) acute myeloid leukaemia (AML) who underwent allogeneic HSCT at our Institution between 2002 and 2011, to verify outcome and to identify factors that can affect long-term outcome. Myeloablative conditioning regimens were used in 48 patients (24 siblings, 24 matched unrelated donor (MUD)), while 30 patients (18 siblings, 12 MUD) received reduced-intensity conditioning. Acute graft versus host disease (GVHD) developed in 37 (47?%) patients, while chronic GVHD occurred in 19 of the 65 evaluable patients (29?%). With a median follow-up time of 5?years, 13 of 78 patients (17?%) are alive and in complete remission (CR), while 64 have died. Cause of death was disease recurrence in 37 patients (58?%), infection in ten patients (16?%) and GVHD in six (9?%). One-year non-relapse mortality was 35?%. In multivariate analysis, performance status ≥80?% WHO and a full-matched donor were associated with a better outcome: these two variables allowed for risk stratification, identifying three groups with significantly different survival after transplant (P?=?0.0001). Considering post-transplant variables, only CR at recovery and development of cGVHD were correlated with a longer survival. Our data confirm the capacity of allogeneic transplant to prolong survival in a significant proportion of extremely high-risk AML patients.     

Subcutaneous adipose tissue blood flow and vasomotion in morbidly obese patients: long term effect of gastric bypass surgery

Since recent findings suggest a relationship between reduction in adipose tissue blood flow (ATBF) and metabolic or vascular complications in obese patients (Ob-pts), increase in ATBF may be considered as a further goal in the treatment of obesity, besides fat mass reduction. Therefore, this preliminary study aimed at assess subcutaneous ATBF and vasomotion in morbidly obese patients and whether sustained weight loss induced by Roux-en-Y gastric bypass (RYGB) affects the same parameters. Using laser-Doppler flowmetry (LDF) and spectral Fourier analysis, subcutaneous ATBF was measured and subcutaneous ATBF oscillations (ATBF-O) were analyzed - within three frequency intervals related to vasomotion - in 16 Ob-pts, before and about one year after RYGB, and in 10 lean, healthy control subjects (CS). Before RYGB, Ob-Pts showed an important reduction in subcutaneous ATBF compared to CS (4.8 ± 2.7 PU vs 79.9 ± 34.5 PU, respectively; p < 0.0001), as well as higher normalized power spectral density (N-PSD) values of subcutaneous ATBF-O, - related to vasomotion. One year after RYGB, sustained weight loss in Ob-pts was associated with a slight but significant increase in subcutaneous ATBF (10.0 ± 6.6 PU, p < 0.05) and with almost complete normalization in N-PSD values of ATBF-O, related to vasomotion, compared to before RYGB. The slight subcutaneous ATBF increase, we observed in Ob-pts after sustained weight loss, moves toward a desirable goal. This finding suggests verifying whether an even more sustained weight loss in Ob-pts could determine a greater increase in subcutaneous ATBF and/or, more importantly, it could also determine a significant increase in visceral ATBF.     

Effects of epidural analgesia on labor length, instrumental delivery, and neonatal short-term outcome

Purpose

We aimed to clarify whether the short-term adverse neonatal outcomes associated with epidural analgesia are due to the epidural analgesia itself or to the instrumental delivery.

Methods

A retrospective case–control study was conducted to evaluate the relationship between epidural analgesia, labor length, and perinatal outcomes. A total of 350 pregnant women at term who delivered under epidural analgesia (cases) were compared with 1400 patients without epidural analgesia (controls).

Results

Vacuum extraction (6.5 vs. 2.9 %) and cesarean section (19.9 vs. 11.1 %) were more frequently performed in the cases than controls (p < 0.001). Using a Kaplan–Meier algorithm, it was determined that the mean lengths of the 1st and 2nd stages of labor and the overall durations of labor and delivery were significantly longer in cases compared with controls. A Cox regression analysis showed that the longer labor remained even after adjustment for parity. The neonatal variables stratified by mode of delivery were not different in cases and controls, except for a slightly lower umbilical arterial pH in spontaneous delivery for the cases group. However, the Apgar scores and umbilical arterial pH were significantly lower in the neonates delivered by vacuum extraction compared with those in the neonates delivered by spontaneous delivery or cesarean section, regardless of whether epidural analgesia was performed. A multivariable analysis showed that vacuum extraction much more consistently affected the arterial pH than the analgesia itself (the β coefficients were ?0.036 for epidural analgesia vs. ?0.050 for vacuum extraction).

Conclusion

Epidural analgesia was associated with slowly progressing labor, thus resulting in an increased rate of instrumental delivery. This instrumental delivery appears to adversely affect the neonatal outcomes more strongly than the analgesia itself.     

MDMA alone affects sensorimotor and prepulse inhibition responses in mice and rats: tips in the debate on potential MDMA unsafety in human activity

Forensic Toxicology - MDMA is a psychoactive drug that has been increasingly abused worldwide, due to its entactogenic properties. However, concerns on its safety exist, particularly regarding its...     

Efficacy of safinamide as add-on therapy after subthalamic nucleus deep brain stimulation in Parkinson disease

Neurological Sciences - Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective surgical treatment for advanced Parkinson’s disease (PD). However, some patients still experience...     

Validation of the DYALS (dysphagia in amyotrophic lateral sclerosis) questionnaire for the evaluation of dysphagia in ALS patients

Neurological Sciences - Dysphagia is a common symptom during the trajectory of ALS, and it can significantly impact on the quality of life and prognosis of patients. Nowadays, no specific tool for...     

Same strategy for pitfalls of radiotherapy in different anatomical districts

Oral mucositis (OM) and radiodermatitis (RD) are serious side effects of radiotherapy (RT), often leading to its suspension, need for analgesics, and enteral/parenteral nutrition. Laser therapy is becoming a recommended treatment option. This prospective study aimed at demonstrating the beneficial effect of class IV laser therapy (HPLT) on RT-induced OM, an off-label use of HPLT to treat RD in breast cancer patients. Fifty-three cancer patients, during/after RT and/or chemotherapy (CT), affected by OM, were treated with HPLT during four consecutive days (970?±?15 nm, 5 W (50 %), 35–6000 Hz, 240 s). Assessment of OM (Grading Objective Scale, WHO-SCALE), pain (visual analogue scale, VAS), functional ability, subjective parameters, and site/severity of OM were recorded over time. Similarly, 27 breast cancer patients affected by RD were treated by HPLT and monitored over time for grade, discomfort, itching, and bleeding. Progressive improvement of WHO-SCALE from day 7 on, and of VAS from day 2 on (p?<?0.000) was registered. All patients’ functional capacity improved on day 4 (p?<?0.05). All subjective parameters improved on day 14 (p?<?0.001) except for voice, which improved on day 21 (p?<?0.000). Ulcerations’ dimension and erythema’s severity significantly decreased in all sites examined (p?<?0.05). Similarly, HPLT proved to be beneficial in managing RD for all the parameters considered (p?<?0.002). Regardless of OM grade/site and of kind/site of tumor, HPLT proved to be effective in healing OM as well as RD. In both cases, effective treatment can improve life quality through a safe, easy, innovative approach. Therefore, HPLT may become an integral part of everyday practice in the management of RT adverse effects.     

Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNA in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value<0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value <0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.