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In recent years, cancer research has highlighted the role of disrupted microbiota in carcinogenesis and cancer recurrence. However, microbiota may also interfere with drug metabolism, influencing the efficacy of cancer drugs, especially immunotherapy, and modulating the onset of adverse events. Intestinal micro-organisms can be altered by external factors, such as use of antibiotics, proton pump inhibitors treatment, lifestyle and the use of prebiotics or probiotics. The aim of our review is to provide a picture of the current evidence about preclinical and clinical data of the role of gut and local microbiota in malignancies and its potential clinical role in cancer treatments. Standardization of microbiota sequencing approaches and its modulating strategies within prospective clinical trials could be intriguing for two aims: first, to provide novel potential biomarkers both for early cancer detection and for therapeutic effectiveness; second, to propose personalized and "microbiota-tailored" treatment strategies., Competing Interests: Declaration of Competing Interest MDM reports honoraria from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, GlaxoSmithKline, Amgen, Merck, Takeda for consultancy or participation to advisory boards and direct research funding from Tesaro/GlaxoSmithKline, institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche. Other 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 © 2024 Elsevier B.V. All rights reserved.)

Background: Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal., Methods: TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS)., Results: From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) (P = .001), opioid use (P = .004), bone metastases number (P < .001), baseline PSA (P = .006), Hb (P < .001), ALP (P < .001) and LDH (P = .002), time between ADT and docetaxel start (P = .018), 3-month PSA (P < .001) and ALP (P < .001), and number of docetaxel cycles (P < .001). OS-related variables were PSA at diagnosis (P = .024), primary tumor treatment (P = .022), baseline pain (P = .015), opioid use (P < .001), bone metastases number (P < . 001), baseline Hb (P < .001), ALP (P < .001) and LDH (P = .001), NLR ratio (P = .039), 3-month PSA (P < .001) and ALP (P < .001) and docetaxel cycles number (P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS., Conclusion: Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy., Competing Interests: Disclosure All authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background : To evaluate the rates of lumbar puncture (LP) in infants with culture-proven sepsis. Study design : We prospectively enrolled 400 infants with early- or late-onset sepsis due to Group B streptococcus (GBS) or Eschericha coli , diagnosed within 90 days of life. Rates of LP and potential variables associated with LP performance were evaluated. Moreover, cerebrospinal fluid (CSF) characteristics and results of the molecular analysis were investigated. Results : LP was performed in 228/400 (57.0%) infants; 123/228 LPs (53.9%) were performed after antibiotic initiation, hampering the ability to identify the pathogen in the CSF culture. However, polymerase chain reaction increased the probability of positive results of CSF analysis compared to microbiological culture (28/79, 35.4% vs. 14/79, 17.7%, p = 0.001). Severe clinical presentation and GBS infection were associated with higher LP rates. The rate of meningitis was 28.5% (65/228). Conclusions : Rates of LP are low in culture-proven neonatal sepsis and antibiotics are frequently given before LP is carried out. Thus meningitis may be underestimated, and the chances of giving an effective therapy to the newborn are reduced. LP should be performed before the start of antibiotics when there is a clinical suspicion of infection.

The effectiveness of "inadequate" intrapartum antibiotic prophylaxis (IAP administered < 4 h prior to delivery) in preventing early-onset sepsis (EOS) is debated. Italian prospective surveillance cohort data (2003-2022) were used to study the type and duration of IAP according to the timing of symptoms onset of group B streptococcus (GBS) and E. coli culture-confirmed EOS cases. IAP was defined "active" when the pathogen yielded in cultures was susceptible. We identified 263 EOS cases (GBS = 191; E. coli = 72). Among GBS EOS, 25% had received IAP (always active when beta-lactams were administered). Most IAP-exposed neonates with GBS were symptomatic at birth (67%) or remained asymptomatic (25%), regardless of IAP duration. Among E. coli EOS, 60% were IAP-exposed. However, IAP was active in only 8% of cases, and these newborns remained asymptomatic or presented with symptoms prior to 6 h of life. In contrast, most newborns exposed to an "inactive" IAP (52%) developed symptoms from 1 to >48 h of life. The key element to define IAP "adequate" seems the pathogen's antimicrobial susceptibility rather than its duration. Newborns exposed to an active antimicrobial (as frequently occurs with GBS infections), who remain asymptomatic in the first 6 h of life, are likely uninfected. Because E. coli isolates are often unsusceptible to beta-lactam antibiotics, IAP-exposed neonates frequently develop symptoms of EOS after birth, up to 48 h of life and beyond.

The optimal timing of surgery after neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is still controversial. Aim of this study was to evaluate the effect of increasing time interval between the end of CRT and surgery on pathological outcomes. This is a retrospective analysis on 114 patients treated with long-course neoadjuvant RT with or without chemotherapy between January 2005 and September 2020. 43 patients underwent surgery within 10 weeks from the end of CRT (1st group), whereas 71 patients underwent total mesorectal excision with a time interval equal or greater than 10 weeks (2nd group). Primary endpoint was pCR (pathological complete response). Secondary endpoints were near pCR (ypT0-1 N0), tumor downstaging (ypT less than cT), nodal downstaging (ypN less than cN), and overall response comparing clinical with pathological TN stage. Overall, the pCR rate was 8.8%, whereas we observed no significantly difference in primary endpoint between the two groups. Considering near pCR, a trend toward significant difference in favor of 2nd group was seen (p = 0.072). Tumor and nodal downstaging rates were 39.5%, 41.9%, 59.2%, and 56.3% in the 1st and 2nd group, respectively, with a statistically significant difference for T category (p = 0.042). Overall response rates (TN stage) showed a trend toward significant difference in favor of patients of the ≥ 10 week group (p = 0.059). Our study suggests that a prolonged time interval between the end of CRT and surgery (≥ 10 weeks) increases pathological response rates., (© 2021. Italian Society of Surgery (SIC).)

Competing Interests: Valeria MerzConsulting or Advisory Role: Amgen Davide MelisiConsulting or Advisory Role: Baxter, Lilly, Evotec, Incyte, iOncturaResearch Funding: Shire, Celgene, Incyte, iOnctura, RocheNo other potential conflicts of interest were reported.

Objective: Group B streptococcus (GBS) early-onset sepsis (EOS) has declined after widespread intrapartum antibiotic prophylaxis. However, strategies for preventing EOS may differ across countries. The analysis of their strategies allows to compare the effectiveness of prevention in different countries and suggests opportunities for improvement. Methods: We compared six western countries. Prevention strategies, incidence rates of EOS and approaches for managing neonates at-risk were analysed. Countries were selected because of availability of recommendations for prevention and sufficient epidemiological data for comparison. Results: Five of six countries recommend antenatal vagino-rectal screening. The decline of GBS cases is relevant in most countries, particularly in those with a screening-based strategy, which have reached incidence rates from 0.1 to 0.3/1000 live births and zero or close to zero mortality in full-term newborns. The recommendation for managing asymptomatic neonates at risk for EOS varies according to gestational age and ranges from observation only to laboratory testing plus empirical antibiotics. Chorioamnionitis (suspected or confirmed) is the main indication for carry out laboratory testing and for administering empirical antibiotics. Conclusions: Wide variations exists in preventing EOS. They depend on national epidemiology of GBS infections, compliance, cost, and feasibility of the strategy. The extreme variability of approaches for managing neonates at risk for EOS reflects the even greater uncertainty regarding this issue, and may explain the persisting, great use of resources to prevent a disease that has become very rare nowadays.

An error inadvertently occurred in the discussion of the original publication when citing the local relapse rates of the EORTC 22881-10882 trial ('boost vs no boost trial').

Accelerated hypofractionated whole-breast radiotherapy (WBRT) is considered a standard therapeutic option for early breast cancer (EBC) in the postoperative setting after breast conservation (BCS). A boost to the lumpectomy cavity may further increase local control. We herein report on the 10-year results of a series of EBC patients treated after BCS with hypofractionated WBRT with a concomitant photon boost to the surgical bed over 4 weeks. Between 2005 and 2007, 178 EBC patients were treated with a basic course of radiotherapy consisting of 45 Gy to the whole breast in 20 fractions (2.25 Gy daily) with an additional boost dose of 0.25 Gy delivered concomitantly to the lumpectomy cavity, for an additional dose of 5 Gy. Median follow-up period was 117 months. At 10-year, overall, cancer-specific, disease-free survival and local control were 92.2% (95% CI 88.7-93.4%), 99.2% (95% CI 96.7-99.7%), 95.5% (95% CI 91.2-97.2%) and 97.3% (95% CI 94.5-98.9%), respectively. Only eight patients recurred. Four in-breast recurrences, two axillary node relapses and two metastatic localizations were observed. Fourteen patients died during the observation period due to other causes while breast cancer-related deaths were eight. At last follow-up, ≥G2 fibrosis and telangiectasia were seen in 7% and 5% of patients. No major lung and heart toxicities were observed. Cosmetic results were excellent/good in 87.8% of patients and fair/poor in 12.2%. Hypofractionated WBRT with concomitant boost to the lumpectomy cavity after BCS in EBC led to consistent clinical results at 10 years. Hence, it can be considered a valid treatment option in this setting.

Background: Data regarding the minimum duration of intrapartum antibiotic prophylaxis (IAP) required for preventing group B Streptococcus (GBS) early-onset sepsis are conflicting. Understanding factors that influence neonatal colonization (NC) might help us understand factors associated with failure of prophylaxis., Methods: This is a 14-month prospective cohort study conducted at a single tertiary care center with a screening-based strategy. Women were enrolled if they had ≥ 35 weeks' gestation and were GBS-positive at the vaginal site on admission. Their neonates were cultured from the throat and rectum at 24-48 h after birth. Colony growth was graded semiquantitatively (from 1+ to 4+). Uni- and multivariate logistic regression analyses were performed to evaluate risk factors for NC., Results: There were 502 neonates, 458 of whom were exposed to IAP. All cases of NC were associated with a lack of IAP exposure (P < 0.01), intrapartum fever ≥ 37.5°C (P < 0.01) and African ethnicity (P < 0.01). In the 458 IAP-exposed neonates, the rates of NC were low and did not vary significantly in the range of less than 1-12 h before delivery (score test for trend of odds, P = 0.13). The only independent factors associated with NC were intrapartum fever ≥ 37.5°C and heavy maternal colonization (P < 0.01 and P = 0.03, respectively)., Conclusions: Heavy maternal colonization, intrapartum fever, African ethnicity and lack of IAP exposure were associated with GBS transmission in neonates born to women who were tested positive on admission. Low rates of NC were found among IAP-exposed neonates irrespective of IAP duration.

Background/aims: The natural history of thyroid function in children with Down's syndrome is relatively unknown. We hypothesized that in these patients the occurrence of thyroid dysfunction rises during development., Methods: Thyroid function was assessed yearly in 145 children with Down's syndrome, all followed from birth up to 10 years of age. Heteroskedastic binary and ordinary logistic regression for repeated measures was used to evaluate the relationship of thyroid function with continuous time., Results: Congenital hypothyroidism was detected in 7% of cases. The probability of acquired thyroid dysfunction increased from 30% at birth to 49% at 10 years (p < 0.001). The subclinical hypothyroidism was nearly stable during the follow-up. The probability of hypothyroidism increased from 7 to 24% at 10 years (p < 0.001). Positive anti-thyroglobulin antibodies were associated with higher odds of more severe hypothyroidism (odds ratio 3.6). Positive anti-thyroid peroxidase antibodies were a better predictor of more severe hypothyroidism (odds ratio 6.1). Diffuse hypoechogenicity on thyroid ultrasound was found in 34 out of 145 children., Conclusion: The probability of thyroid dysfunction increasing during development is higher than previously reported. Such children should be carefully monitored annually to early identify thyroid dysfunction., (© 2014 S. Karger AG, Basel.)

Objective: The accuracy of the SenseWear Pro2 Armband (SWA) in estimating resting energy expenditure (REE) in children and adolescents with obesity, using indirect calorimetry (IC) as a reference was evaluated., Design and Methods: REE was assessed using both the SWA and IC in 40 obese subjects (26 M/14 F, age 11.5 ± 2.57 years, z-score BMI 3.14 ± 0.53). The agreement between methods was assessed by the Bland-Altman procedure. The relationship between REE assessments and patients' characteristics was also analyzed., Results: SWA- and IC-derived estimates of REE showed a significant correlation (r = 0.614; P < 0.001), but the SWA overestimated mean REE by 13% (P < 0.001). Age and kilogram of fat-free mass (kg-FFM) were significantly correlated with both REE estimation by SWA (r = 0.434 and r = 0.564, respectively) and IC (r = 0.401 and r = 0.518, respectively). Only kg-FFM was demonstrated to be the main predictor factor of REE variability (r(2) 79% SWA; 75% IC)., Conclusions: The SWA overestimated mean REE in childhood obesity, suggesting that the SWA and IC are not yet interchangeable methods. This would require improving the SWA by developing better algorithms for predicting REE and, probably, bias in each individual REE could be reduced by an adjustment for subjects' kg-FFM., (Copyright © 2013 The Obesity Society.)

Neonatal bacterial meningitis (NM) continues to be a serious disease with an unchanging rate of adverse outcome of 20-60%, despite a worldwide decline in mortality. The 3 major pathogens in developed countries are: Group B streptococcus, gram negative rods and Lysteria monocytogenes. Signs and symptoms of NM may be subtle, unspecific, vague, atypical or absent. In order to exclude NM, all infants with proven or suspected sepsis should undergo lumbar puncture. Positive culture of cerebrospinal fluid may be the only way to diagnose NM and to identify the pathogen, as CSF parameters Smay be normal at early stages and NM may occur frequently (up to 30% of cases) in the absence of bacteraemia. When NM is suspected, treatment must be aggressive, as the goal is to achieve bactericidal concentration of antibiotics and to sterilize CSF as soon as possible. Antibiotics should be administered intravenously, at the highest clinically validated doses. Empiric antibiotic treatment should include agents active against all main pathogens; currently the recommended empiric treatment of NM is ampicillin, plus an aminoglycoside and a third-generation cephalosporn. Therapy should be reassessed after cultures and antibiotic susceptibility is available. Prevention of neonatal sepsis, early recognition of infants at risk, prompt treatment and future adjunctive therapies will improve prognosis. Finally, we present the first preliminary Italian data on GBS meningitis. Data are obtained from an area-based study conducted In Emilia-Romagna during 2003 to 2009.

Background: Lung cancer is the leading cause of cancer death in men worldwide; most cases are not suitable for radical surgery at diagnosis and palliative treatment remains the primary goal of therapy. Cisplatin and gemcitabine are among the most active cytotoxic agents for the treatment of non-small cell lung cancer (NSCLC): they have non-overlapping toxicity and preclinical studies have demonstrated their potential synergistic interaction., Patients and Methods: The aims of the present study were to assess the activity and tolerability of cisplatin 80 mg/m2 on day 1, combined with gemcitabine 1000 mg/m2 on days 1 and 8, administered every 3 weeks. A total of 46 consecutive patients with advanced NSCLC entered this study; all of them were evaluable for toxicity and for activity., Results: According to an intent-to-treat analysis, 15 patients attained a partial response (33%), 9 (20%) obtained a disease stabilisation and 22 (47%) progressed. This regimen appeared to be modestly toxic, with grades 3-4 leukopenia and thrombocytopenia observed in 10% and 6% of cases respectively; grade 3 vomiting appeared in 12 patients (26%) and grade 3 mucositis in 1 patient. The median time-to-progression and overall survival were 200 and 400 days, respectively., Conclusion: Our study of gemicitabine + cisplatin on stage IV NSCLC patients achieved favourable results in terms of toxicity and overall survival.

Purpose: To ascertain the best surgical technique for fixating an intraocular lens (IOL) in the posterior chamber in the absence of capsular support., Setting: From the Institute of Ophthalmology, Pavia University, Pavia, Italy., Methods: Using the SFVT System, the phases of IOL fixation were evaluated in cadaver eyes. In addition, IOLs were implanted in the posterior chamber in 340 eyes of patients without capsular support. One of several IOL fixation methods was used; IOL power was calculated using the same parameters as when the lens is positioned in the sulcus. Mean follow-up was 3.5 years (range 2 months to 5 years)., Results: Intraocular lens placement was accurate only when the loops were positioned in the sulcus, with the best approach being internal with suspension sutures placed at 3 and 9 o'clock. In most cases, refractive results were good; 152 eyes were within +/- 1.00 diopter of the predicted value., Conclusion: In eyes without capsular support, IOL implantation in the sulcus was possible only when sutures were placed exactly through the sulcus. An internal approach using suspension sutures at 3 and 9 o'clock gave the best results.

The authors present 15 cases of hyp arthroplasty implanted in patients affected with necrosis of the femoral head, which were undergoing periodic hemodialitic treatment, or with renal transplants. Ceramic-ceramic prostheses were prevalently used and only in 1 case was a metal-polyethylene prosthesis used. Because of precarious mineralization a cemented prosthesis was implanted in dialyzed patients; in renal transplants, instead, cemented or cementless prosthesis were used depending on the state of the bone. There was a high percentage of excellent results after 2-8 years (87%), and this confirms the validity of surgical indications for the use of arthroplasty in hips affected with epiphyseal necrosis in order to favor functional recovery: considering the young age od the patients, this helps them to go back to being a part of society, and to recover psychologically.

A total of 18 hemodialyzed patients submitted to surgery for the treatment of carpal tunnel syndrome are examined. In all of the cases pre- and postoperative EMG and biopsy were performed. Six months after surgery all of the patients showed improved pain symptoms, in 66% there was good recovery of sensitivity and of the function of the hand: these results were confirmed by EMG monitoring. In all of the biopsies amyloid deposits, particularly diffused in the tendinous and nervous sheaths, were observed. At 2-year follow-up 75% of the patients showed recurrence of pain symptoms. Thus, surgery does not seem to definitively resolve symptoms.