A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population

<p>Abstract</p> <p>Background</p> <p>The purpose of this study is to analyze the combined effects of selected <it>p</it>53 and <it>p</it>73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.</p> <p>Methods</p> <p>Two hundred and eighty-three cases and 295 hospital controls were genotyped for <it>p</it>53 polymorphisms on exon 4 (Arg72Pro), intron 3 and 6, and <it>p</it>73 G4C14-to-A4T14. Their association with SCCHN was estimated using a logistic regression analysis, while a multinomial logistic regression approach was applied to calculate the effect of the selected polymorphisms on SCCHN different sites (oral cavity, oropharynx, hypopharynx and larynx). We performed an haplotype analysis of the <it>p</it>53 polymorphisms, and a gene-gene interaction analysis for the combined effects of <it>p</it>73 G4C14-to-A4T14 and <it>p</it>53 polymorphisms.</p> <p>Results</p> <p>We found a significant increased risk of SCCHN among individuals with combined <it>p</it>73 exon 2 G4A and <it>p</it>53 intron 3 variant alleles (OR = 2.22, 95% CI: 1.08–4.56), and a protective effect for those carrying the <it>p</it>53 exon 4-<it>p</it>53 intron 6 diplotype combination (OR = 0.67; 95% CI: 0.47–0.92). From the gene-environment interaction analysis we found that individuals aged < 45 years carrying <it>p</it>73 exon 2 G4A variant allele have a 12.85-increased risk of SCCHN (95% CI: 2.10–78.74) compared with persons of the same age with the homozygous wild type genotype. Improved survival rate was observed among <it>p</it>53 intron 6 variant allele carriers (Hazard Ratio = 0.51 (95% CI: 0.23–1.16).</p> <p>Conclusion</p> <p>Our study provides for the first time evidence that individuals carrying <it>p</it>53 exon 4 and <it>p</it>53 intron 6 variant alleles are significantly protected against SCCHN, and also shows that an additional risk is conferred by the combination of <it>p</it>73 exon 2 G4C14-to-A4T14 and <it>p</it>53 intron 3 variant allele. Larger studies are required to confirm these findings.</p

Gefitinib in Non Small Cell Lung Cancer

Gefitinib is an oral, reversible, tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) that plays a key role in the biology of non small cell lung cancer (NSCLC). Phase I studies indicated that the recommended dose of gefitinib was 250 mg/day. Rash, diarrhea, and nausea were the most common adverse events. The positive results obtained in early phase 2 clinical trials with gefitinib were not confirmed in large phase 3 trials in unselected patients with advanced NSCLC. The subsequent discovery that the presence of somatic mutations in the kinase domain of EGFR strongly correlates with increased responsiveness to EGFR tyrosine kinase inhibitors prompted phase 2 and 3 trials with gefitinib in the first line-treatment of EGFR-mutated NSCLC. The results of these trials have demonstrated the efficacy of gefitinib that can be now considered as the standard first-line treatment of patients with advanced NSCLC harbouring activating EGFR mutations

Infected pancreatic necrosis : outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

Peer reviewe

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P &lt; .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Embryo quality before and after slow freezing: Viability, implantation and pregnancy rates in 627 single frozen-thawed embryo replacement cycles following failure of fresh transfer

Frozen embryo transfer cycles are now common practice, however, various aspects regarding the potential of frozen embryos remain unclear. The main goal of the present study was to assess embryo quality before and after slow freezing procedure, and more specifically blastomere loss and embryo quality as indicator of viability. A single center retrospective analysis of single frozen-thawed embryo replacements (s-FER) was performed. The embryo quality before and after slow freezing and thawing, implantation, and pregnancy rates were recorded. One hundred and twenty seven s-FER were included in the final analysis. The probability of achieving an ongoing pregnancy was significantly associated with embryo quality and the percentage of blastomere loss after thawing. Considering thawed embryos, a non-significant difference in term of implantation rate was observed, regardless to their post-thawing quality and the percentage of blastomeres loss. In conclusion, current data suggest that thawed embryos are capable of implantation regardless of their morphological quality and the degree of cryoinjury sustained

Evaluation of disposable pre-impregnated wipes versus a standard two-step protocol for cleaning and disinfection of high-touch surfaces in intensive care

Aim(s)/Objective(s):Toevaluatetheeffectivenessofpre-impregnated wipesinreducingenvironmental bacterialburdenwhencompared to the current standard protocol (SP). Method(s): High-touch surfaces in a 12-bed Intensive Care Unit were cleanedanddisinfectedeitherbythedailystandardtwo-stepprotocol, application of an alcohol-based detergent Keradet (Kiehl), followed by a chlorine-based disinfectant Antisapril 2% (Angelini), or by using disposable wipes impregnated with quaternary ammonium compounds/Biguanide (Clinell Universal Wipes, GAMA). Effectiveness in reducingmicrobialburdenof hightouch near-patient surfaces was assessed by a contact plate method on five sites immediately pre- procedure and post- at 0.5, 2.5, 4.5 and 6.5 hours. The study was repeated five times over three months, sampling 11 beds for each protocol (560 sampling sites). Results: Pre-impregnated wipes demonstrated a decrease in mean TotalBacterialCount (TBC)from43to16CFU/24 cm2 (63.9%)after0.5 hours vs. a reduction from 27 to 16 CFU/24 cm2 (40.3%) for the SP. In subsequent 2.5, 4.5 and 6.5-hour tests, mean TBCs decreased respectively by 64.1%, 65.6% and 74.1% with disposable wipes, while for SP methods, TBCs showed increases of 8.3%, 20.7% and 24.3%. According to the Italian hygiene standard (ISPESL, 2009), when using pre-impregnated wipes 14 of 180 sites of sites showed TBC >50 CFU/ 24cm2 (Hygiene Failures) whereas for SP 32 of 176 sites were classed as failed (Chi squared, p<0.05). Discussion and/or Conclusion(s): Disposable wipes used on nearpatient inanimate surfaces provide a more effective alternative to the usualtwo-stepprocedures,consideringthepotentialresidualactivit

Esophageal achalasia with recurrent aspiration pneumoniae treated by laparoscopic Heller myotomy

We report here a case of aspiration pneumonia diagnosed in a 69-year old Caucasian woman, presenting with acute respiratory failure, left pleural effusion, and right posterior basal lung consolidation revealed by chest imaging. In the last ten years, she has been hospitalized several times for community-acquired pneumonia. For this reason, and the presence of dysphagia during the admission to our respiratory ward, we suspected recurrent aspiration pneumonia which was found secondary to achalasia. At 15-month follow up after laparoscopic Heller myotomy with anti-reflux procedure the patient has remained asymptomati