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Objectives: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors., Material and Methods: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed., Results: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association., Conclusions: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aims: To evaluate the effects of high intra-abdominal pressure (IAP) during hyperthermic intraperitoneal chemotherapy (HIPEC) on cisplatin uptake by residual tumor and normal tissues, pharmacokinetics, and short-term surgical outcomes., Patients & Methods: Patients with peritoneal metastasis from colorectal cancer or pseudomyxoma peritonei were randomized to closed-abdomen HIPEC with low-IAP or high-IAP, after complete cytoreduction. High-IAP was obtained increasing the volume of perfusate maintaining constant the cisplatin concentration (42 mg/L). We determined the Platinum concentration using an Inductive Coupled Plasma Mass Spectrometry System. Randomization was stratified according to tumor type. To consider the multiple sampling in the three tissues types of interest, we performed linear mixed models to assess the differences of cisplatin concentration between study arms. We also compared AUC perfusate/plasma ratios (Wilcoxon-Mann-Whitney) and perioperative severe complication rates (chi-square) between study arms., Results: 38 cases were randomly assigned to IAP arms (n = 19 each). Median IAPs were 19 mmHg and 11 mmHg in the high and low arms, respectively. Cisplatin concentrations did not differ in the tumor residual tissues and in the muscular fascia [22.8 ng/mg (SD: 25.5) vs. 15.9 ng/mg (SD: 13.3), p = 0.181] and [50.3 ng/mg (SD: 40.1) vs. 42.0 ng/mg (SD: 38.3), p = 0.426, respectively], whereas in the mesenteric peritoneum it did [5.4 ng/mg (SD: 7.82) vs. 2.7 ng/mg (SD: 2.9), p = 0.048]. Pharmacokinetic advantage did not differ between the two arms. High-IAP did not increase perioperative severe complications rate (NCI-CTCAE.v3)., Conclusions: high-IAP HIPEC increases cisplatin distribution in the mesenteric peritoneum, is safe, and could be considered to obtain microscopic cytoreduction., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: cytoreduction surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is currently the standard of care for some peritoneal surface malignancies. There is experimental evidence supporting that high Intra Abdominal Pressure (IAP) during HIPEC could enhance the uptake of drugs by tumor tissues. However, few papers are describing the hemodynamic and respiratory effects of increased IAP during HIPEC., Aims: to evaluate the hemodynamic and respiratory association with different IAPs during HIPEC., Methods: This is part of an IRB board approved prospective randomized controlled trial conducted at The National Tumor Institute of Milan from 2014 to 2017 (NCT0294979). Patients diagnosed with Pseudomyxoma (PMP) or Peritoneal Metastasis of Colorectal Cancer (PM-CRC) were submitted to CRS and then randomized to receive low IAP (8-12 mmHg) or high IAP (18-22 mmHg) HIPEC. Hemodynamic and respiratory data were collected in eight different time-points during the whole procedure., Results: 33 patients (n low = 15, n high = 18) with PM-CRC and PMP were analysed. The mean IAP in the low IAP HIPEC group was 11.4 mmHg (SD: 2.5) and 18.1 mmHg (SD: 2.5) in the high IAP HIPEC group (p«0.001). There was no difference in the hemodynamic parameters between both groups, except for the central venous pressure (CVP) that was significantly higher in the high IAP group (p = 0.006). High IAP was well tolerated in the experimental arm with no hemodynamic and ventilation instability observed during the intervention., Conclusion: We conclude that high IAP at the level of 18-22 mmHg during HIPEC has no significant hemodynamic parameters difference, being feasible and safe in our study., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: We report the results of an Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study on the treatment of testicular germ cell tumors (TGCT) with a pediatric PEB (pPEB) regimen (cisplatin 25 mg/m 2 daily on days 1-4; etoposide 100 mg/m 2 daily on days 1-4; bleomycin 15 mg/m 2 on day 2, once per cycle)., Methods and Materials: Male patients under 18 years old with malignant TGCT were enrolled for a second national prospective protocol. All patients underwent orchiectomy at diagnosis. Those with Stage I received no chemotherapy; those with Stage II-III disease received three cycles of pPEB; and those with Stage IV received four cycles. After chemotherapy, resection of radiologically-evident residual disease was recommended. The main study end-points were overall survival and relapse-free survival., Results: Ninety-nine boys from 0.5 to 17.8 years old (median 15.4 years) were evaluable, and staged as follows: 58 Stage I (59%), 7 Stage II (7%), 14 Stage III (14%), and 20 Stage IV (20%). With a median follow-up of 59 months (range 4-165 months), 5-year relapse-free survival (95% CI) was 73% (65%-83%) for the whole sample, 65% (53%-79%) for Stage I patients, and 86% (75%-98%) for Stage II-IV patients. Five-year overall survival (95% CI) was 99% (97%-100%)., Conclusions: We confirmed a good prognosis for malignant TGCT in children and adolescents. Reducing the number of chemotherapy cycles for Stage II-III disease does not seem to negatively affect survival outcomes., (Copyright © 2018. Published by Elsevier Inc.)

Background: Preterm infants complete their development in Neonatal Intensive Care Unit being exposed to environmental stimuli that lead to the early maturation of the sensory systems. It is known that the fetus perceives sounds and reacts to them with movements since the 26th-28th week of gestational age. Maternal voice represents a source of sensory stimulation for the fetus., Aims: To investigate the effect of the exposure to maternal voice, administered by bone conduction, on preterm infants autonomic and neurobehavioral development., Study Design: Longitudinal, explorative, case control study., Subjects: 71 preterm infants with birth weight <1500g, born adequate for gestational age, Outcome Measures: vital and neurobehavioral parameters at term, neurofunctional assessment at 3 and 6months of corrected age., Results: Infants in the treatment group had lower heart rate values and a higher proportion of stable skin color at each study point as compared to the control group. The scores in the visual attention performance and in the quality of the general movements at term were better in the treatment group than in the control one. Neurofunctional assessment score at 3months of corrected age was higher in the treatment group whereas no difference between the two groups was detected at 6months of corrected age., Conclusions: Early exposure to maternal voice exerts a beneficial effect on preterm infants autonomic and neurobehavioral development., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Epigenetics is believed to play a role in Alzheimer's disease (AD). DNA methylation, the most investigated epigenetic hallmark, is a reversible mechanism that modifies genome function and chromosomal stability through the addition of methyl groups to cytosine located in CpG dinucleotides to form 5 methylcytosine (5mC). Methylation status of repetitive elements (i.e. Alu, LINE-1 and SAT-α) is a major contributor of global DNA methylation patterns and has been investigated in relation to a variety of human diseases. However, the role of methylation of repetitive elements in blood of AD patients has never been investigated so far. In the present study, a quantitative bisulfite-PCR pyrosequencing method was used to evaluate methylation of Alu, LINE-1 and SAT-α sequences in 43 AD patients and 38 healthy donors. In multivariate analysis adjusting for age and gender, LINE-1 was increased in AD patients compared with healthy volunteers (ADs: 83.6%5mC, volunteers: 83.1%5mC, p-value: 0.05). The group with best performances in mini mental state examination (MMSE) showed higher levels of LINE-1 methylation compared to the group with worst performances (MMSE>22: 83.9%5mC; MMSE≤22: 83.2%5mC; p=0.05). Our data suggest that LINE-1 methylation may lead to a better understanding of AD pathogenesis and course, and may contribute to identify novel markers useful to assess risk stratification. Further prospective investigations are warranted to evaluate the dynamics of DNA methylation from early-stage AD to advanced phases of the disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)