Data of postoperative complications related to fibrinogen-to-albumin ratio in pancreatic resections.

Pancreatic surgery is one of the surgeries burdened with the highest mortality and morbidity rate. This is due both to the aggressive biological nature of the pathology affecting the organ and to the technical difficulties associated with surgery. A further aspect on which research is focusing is represented by inflammation related to oncological pathology. Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival (OS) in malignant tumors. Inflammatory markers had demonstrated also a role in the prediction of postoperative complication after pancreatic surgery. We speculate that FAR, as an easily available, cost-effective, and non-invasive prognostic indicator for pancreatic cancer patients, could help to identify patients at increased risk of postoperative pancreatic fistula (POPF). We therefore retrospectively analyzed the data relating to 117 pancreatic resections relating direct and indirect markers of inflammation with the incidence of post-operative complications.

Frailty Is Associated with Impaired Diabetic Foot Ulcer Healing and All-Cause Re-Hospitalization.

BACKGROUND: Diabetic Foot Ulcers (DFUs) are a common and feared complication of type 1 and type 2 diabetes. People with DFUs often present a significant clinical complexity due to multimorbidity, frailty, polypharmacy, and disabling conditions. Frailty, defined using the accumulation of health deficits model, has shown to predict worsening health status, hospitalizations, and death in older persons. There are no clinical studies, to date, that have examined the prevalence and effect of frailty on DFUs outcomes. The aim of our study was to explore the impact of frailty on DFUs healing and re-hospitalization in a cohort of patients hospitalized with DFUs. DESIGN: prospective cohort study. SETTING AND PARTICIPANTS: The frailty status of 76 consecutive hospitalized patients with DFUs was assessed by using the Frailty Index (FI). MEASUREMENTS: The primary outcome was the non-healing of the DFU. Secondary outcome was re-hospitalization events (for any cause) within 6 months from hospital discharge. Frailty was defined as FI>0.25. RESULTS: Out of 76 patients (median age 65 years, range 31-84), 56 (74%) were frail. At six months, 81.5% of frail patients had non-healing of the DFU compared to 55% in non-frail patients (p=0.02). The rate of of re-hospitalization was also higher in frail compared to non-frail (90.3% vs 54%, respectively; p=0.01) patients. In multivariable analyses, frailty was significantly associated with a more than fivefold increased risk of DFU non-healing [odds ratio 5.54 (95% confidence interval 1.28-23.91), p=0.02]. Similarly, re-hospitalization was also significantly higher in frail patients compared to the non-frail ones. CONCLUSIONS: In hospitalized patients with DFUs, frailty was highly prevalent. Frailty emerged as an independent risk factor for DFU non-healing and re-hospitalization events. Patients with DFUs require a comprehensive assessment of their frailty status which would enable personalization of their management and interventions.

Superresolution Linear Optical Imaging in the Far Field.

The resolution of optical imaging devices is ultimately limited by the diffraction of light. To circumvent this limit, modern superresolution microscopy techniques employ active interaction with the object by exploiting its optical nonlinearities, nonclassical properties of the illumination beam, or near field probing. Thus, they are not applicable whenever such interaction is not possible, for example, in astronomy or noninvasive biological imaging. Far field, linear optical superresolution techniques based on passive analysis of light coming from the object would cover these gaps. In this Letter, we present the first proof-of-principle demonstration of such a technique for 2D imaging. It works by accessing information about spatial correlations of the image optical field and, hence, about the object itself via measuring projections onto Hermite-Gaussian transverse spatial modes. With a basis of 21 spatial modes in both transverse dimensions, we perform two-dimensional imaging with twofold resolution enhancement beyond the diffraction limit.

Carboplatin-paclitaxel compared to Carboplatin-Paclitaxel-Bevacizumab in advanced or recurrent endometrial cancer: MITO END-2 - A randomized phase II trial.

OBJECTIVE: Increased Vascular Endothelial Growth Factor Receptor (VEGF) expression in endometrial cancer (EC) is associated with a poor prognosis. Preliminary clinical data reported Bevacizumab effectiveness in EC both as single agent and in combination with chemotherapy. METHODS: In a phase II trial, patients with advanced (FIGO stage III-IV) or recurrent EC were randomized to receive Carboplatin-Paclitaxel standard dose for 6-8 cycles vs Carboplatin-Paclitaxel and Bevacizumab 15 mg/kg in combination with chemotherapy and maintenance until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS). RESULTS: 108 patients were randomized; PFS (10.5 vs 13.7 months, HR 0.84 p = 0.43), overall response rate (ORR 53.1% vs 74.4%) and overall survival (OS) (29.7 vs 40.0 months, HR 0.71 p = 0.24) resulted in a non-significant increase in Bevacizumab treated patients. The PFS increase became significant when an exploratory analysis with the Breslow test was used. Moreover, patients treated with Bevacizumab experienced a significant increase in 6-month disease control rate (70.4% vs 90.7%). Cardiovascular events were more frequent in the experimental arm ("de novo" grade ≥2 hypertension 21% vs 0% and grade ≥2 thromboembolic events 11% vs 2% in the Bevacizumab vs standard treatment arm, respectively). CONCLUSIONS: Bevacizumab combined with chemotherapy in the treatment of advanced/recurrent EC failed to demonstrate a significant increase in PFS in the MITO END-2 trial. Nevertheless, these preliminary data suggests some effectiveness of the antiangiogenic agent which merits further exploration in a larger population with a better molecular characterization.

Elevated obstructive sleep apnoea risk score is associated with poor healing of diabetic foot ulcers: a prospective cohort study.

AIMS: To assess the prevalence of risk factors for obstructive sleep apnoea in people with diabetic foot ulcers and to determine whether this risk predicts diabetic foot ulcer healing. METHODS: We studied 94 consecutive people (69% men) with diabetic foot ulcers (Type 2 diabetes, n=66, Type 1 diabetes, n=28) attending a university hospital foot unit. All participants were screened for obstructive sleep apnoea using the STOP-BANG questionnaire, with a score ≥4 identifying high risk of obstructive sleep apnoea. The primary outcome was poor diabetic foot ulcer healing, defined as diabetic foot ulcer recurrence (diabetic foot ulcers which healed and re-ulcerated in same anatomical position) and/or diabetic foot ulcer persistence (no evidence of healing on clinical examination). All participants were evaluated at 12 months. RESULTS: Of the 94 participants, 60 (64%) had a STOP-BANG score ≥4. Over 12 months, 27 participants with a score ≥4 had poor diabetic foot ulcer healing as compared to seven with a score <4 (45% vs 20.5%; P=0.025). A STOP-BANG score ≥4 significantly increased the relative risk of poor healing more than twofold, independently of other risk factors in multivariable analyses. CONCLUSIONS: There is a high prevalence of features and risk of obstructive sleep apnoea in people with diabetic foot ulcers. A STOP-BANG score ≥4 predicts poor diabetic foot ulcer healing. Obstructive sleep apnoea may be a potential, modifiable risk factor/treatment target to improve diabetic foot ulcer outcomes.

Peripheral neuropathy in diabetes: it's not always what it looks like.

BACKGROUND: Hereditary Neuropathy with liability to Pressure Palsies (HNPP) is an autosomal dominant neuropathy, associated with deletion of the Peripheral Myelin Protein-22 (PMP-22) gene, causing recurrent painless palsies with age of onset between 10 and 30 years old. Only a few cases of Type 2 Diabetes and HNPP have been described and the coexistence of HNPP and Type 1 diabetes has never been reported. CASE REPORT: A 54-year old man with a history of Type 1 diabetes, managed with continuous subcutaneous insulin infusion (CSII), presented with deterioration of long-standing motor and sensory symptoms, previously attributed to golfer's elbow, diabetic neuropathy and spinal degenerative disease. He had multilevel severe spine degenerative changes and L4/L5 and L5/S1 root impingements with a L4/L5 discectomy performed when he was 25 years old. On physical examination he had normal power and distal hypoaesthesia of the digits and plantar aspect of the feet. Investigations revealed normal full blood count, liver and renal function, electrolytes, vitamin B12 and serum folate. He suffered from primary hypothyroidism and thyroid function tests indicated adequate levothyroxine replacement. Nerve conduction studies revealed a generalized demyelinating sensorimotor neuropathy, with more severe involvement of nerves over entrapment sites. Further history that his father suffered from episodes of weakness and numbness was elicited. Genetic analysis revealed one copy of the PMP22 gene at 17p11.2 confirming the diagnosis of HNPP. CONCLUSION: In people with diabetes the evaluation of peripheral neuropathy should include a careful history, a comprehensive physical examination, blood tests and in some cases nerve conduction studies and genetic testing.

Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial.

BACKGROUND: Current evidence suggest that trabectedin is particularly effective in cells lacking functional homologous recombination repair mechanisms. A prospective phase II trial was designed to evaluate the activity of trabectedin in the treatment of recurrent ovarian cancer patients presenting BRCA mutation and/or BRCAness phenotype. PATIENTS AND METHODS: A total of 100 patients with recurrent BRCA-mutated ovarian cancer and/or BRCAness phenotype (≥2 previous responses to platinum) were treated with trabectedin 1.3 mg/mq i.v. q 3 weeks. The activity of the drug with respect to BRCA mutational status and to a series of polymorphisms [single-nucleotide polymorphisms (SNPs)] involved in DNA gene repair was analyzed. RESULTS: Ninety-four were evaluable for response; in the whole population, 4 complete and 33 partial responses were registered for an overall response rate (ORR) of 39.4. In the platinum-resistant (PR) and -sensitive (PS) population, an ORR of 31.2% and 47.8%, and an overall clinical benefit of 54.2% and 73.9%, respectively, were registered. In the whole series, the median progression-free survival (PFS) was 18 weeks and the median overall survival (OS) was 72 weeks; PS patients showed a more favorable PFS and OS compared with PR patients. BRCA gene mutational status was available in 69 patients. There was no difference in ORR, PFS and OS according to BRCA 1-2 status nor any association between SNPs of genes involved in DNA repair and NER machinery and response to trabectedin was reported. CONCLUSIONS: Our data prospectively confirmed that the signature of 'repeated platinum sensitivity' identifies patients highly responsive to trabectedin. In this setting, the activity of trabectedin seems comparable to what could be obtained using platinum compounds and the drug may represent a valuable alternative option in patients who present contraindication to receive platinum. EUDRACT NUMBER: 2011-001298-17.

Non smoking for successful aging: therapeutic perspectives.

The smoke of cigarettes represents an important accelerator of the aging process, and there is no doubt that smoke is an important risk factor for many diseases, in particular for cardiovascular, neoplastic and respiratory diseases. Smoking plays an important role also in the development of other pathological conditions being particularly frequent in geriatric ages, such as dementia, osteoporosis, diabetes, erectile dysfunction, senile macular degeneration, nuclear cataract and alterations of skin. This means that smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autonomy. Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. The first requirement of stopping smoking certainly is the motivation of the smoker himself to do this, since without this motivation any attempt is futile. Today numerous quitting strategies exist, either of pharmacological or non-pharmacological type, which are also advantageous for the elderly person. Approved pharmacological treatments include nicotine replacement therapies, bupropion, drugs targeting cannabinoid receptors and newer pharmacological approaches including the selective nicotinic partial agonists. Varenicline, an alpha4 beta2 nicotinic acetylcoline receptor partial agonist, is the most recently agent approved for smoking cessation. This drug works by reducing the strength of the smoker's urge to smoke and by relieving withdrawal symptoms. The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioural and/or cognitive counselling to improve abstinence rates.

Smoking, aging and the centenarians.

The smoke of cigarettes represents an important accelerator of the aging process, both directly through complex mechanisms mediated prevalently by excessive formation of free radicals, and indirectly by favoring the appearance of various pathologies in which smoke is a recognized risk factor. This means that smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autosufficiency. Smoking is an important risk factor for many diseases, such as cancer, cardiovascular and respiratory diseases. These are also the main causes of death in the industrialized Countries, where the habit of smoking is also largely diffused. Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. Therefore, cigarette smoking is opposing the longevity, particularly the extreme one, as it is confirmed by the observations obtained on centenarians. Among them, smoking is extremely rare, and even when it occurs among them, it is correlated almost exclusively to bad health conditions and non-autosufficiency, indicating that it compromises health status and the quality of life even in extremely long living subjects. Considering the demonstrated beneficial effects of suspension of smoking, all practitioners and geriatricians in particular, should promote the abstinence from smoking as a behavioral norm for a correct life style. Non-smokers can delay the appearance of diseases and of the aging process, thus attaining longevity; further, non-smoking habit allows genetically predisposed subjects to reach the extreme longevity and maintain an acceptable health status and autosufficiency.

Vascular aging and geriatric patient.

Advancing age is associated with changes in structure and function of different segments of the vascular system and is the dominant risk factor for cardiovascular diseases. The oxidative stress represents a key event of vascular aging, mainly characterized by endothelium dysfunction and reduced arterial elasticity. Age-related changes include intimal and medial thickening, arterial calcification, increased deposition of matrix substances, thus leading to a reduced compliance and increased wall stiffness, that significantly contributes to an increase in systolic blood pressure. Frail elderly patients, because of their complex clinical presentations and needs, require a special approach: the comprehensive geriatric assessment, a multidimensional process intended to determine medical, psychosocial and functional capabilities and problems in order to develop a plan for treatment and continued care. All physicians, and geriatricians in particular, must, therefore, educate their patients to healthy lifestyle to prevent or delay vascular aging, cardiovascular diseases, and to maintain a good quality of life and increase life expectancy.

Expander elements in craniofacial surgery: an experimental study in rabbits.

With the inception of craniofacial surgery elaborate surgical procedures were introduced for the treatment of craniosynostosis. Recently the use of implantable springs to aid simple strip craniectomies for these conditions has been described. Having shown the feasibility of using springs for dynamic skull reshaping, several questions remain to be answered, all of them about how to control the spring action clinically. One of the most important questions concerns force. The purpose of this study was to evaluate experimentally the effect of two springs of different strengths on the growth of rabbit calvaria after strip craniectomy. Thirty-two 6-week-old rabbits were randomised into one of four groups: sham-operation where only amalgam markers were inserted after subperiostal dissection; strip craniectomy of the sagittal suture, no expansion; strip craniectomy of the sagittal suture and insertion of an expander element made of titanium molybdenum alloy (TMA); and strip craniectomy sagittal suture and insertion of an expander element made of stainless steel (SS). SS springs delivered a range of forces from 2.42-2.18 N, whereas the TMA expander elements delivered a range from 1.39-1.09 N. The parietal bone marker separation after 12 weeks was 4.9 mm in the TMA group and 7.4 mm in the SS group. This resulted in a significant increase of the calvarian height compared with control groups. Histological examination showed intramembranous bone formation in the bone gap in all groups.

Nitric oxide inhibits neutrophil adhesion during experimental extracorporeal circulation.

BACKGROUND: Myocardial and pulmonary injuries often occur after cardiopulmonary bypass, mediated in part by neutrophil activation and adhesion to endothelial cells. The effects of nitric oxide (NO) administration on neutrophil adhesion to endothelial cells after simulated extracorporeal circulation were investigated. METHODS: Two identical extracorporeal circulation circuits were primed with fresh human blood and circulated for 2 h at 37 degrees C. Nitric oxide at a 40-ppm concentration was added to one of the oxygenators in each pair. Neutrophil CD11b/CD18 expression and their adhesion to human umbilical vein endothelial cell monolayers were assayed in leukocytes isolated from samples drawn from the circuit 30, 60, 90, and 120 min after circulation began. In another series of experiments, blocking monoclonal antibodies to both neutrophil CD11b and CD18 were incubated with polymorphonuclear leukocytes after removal from the circuit before the adhesion assay. RESULTS: After 60 min of circulation, the neutrophils from NO-treated circuits showed significantly reduced CD11b/CD18 surface expression compared with the control group. There was also a significant reduction in neutrophil-endothelial adhesion in the NO group after 120 min of circulation. Monoclonal antibodies to both CD11b and CD18 significantly inhibited the adhesion of polymorphonuclear leukocytes at endothelial cells after 120 min of circulation. CONCLUSIONS: These results confirm that neutrophil activation occurs during cardiopulmonary bypass. The addition of NO to the circuits of extracorporeal circulation significantly affects neutrophil adhesion to endothelial cells.

[Analysis of the quality of death certificates for neoplasms in the province of Ragusa]. / Analisi della qualità dei certificati di morte per neoplasia in provincia di Ragusa.

The reliability of the death certificates issued in Ragusa for 379 of the 909 cancer patients registered in 1986 by the Ragusa Cancer Registry, who had died within 31 october 1988, was investigated. Data were available for 365 cases deceased. A consistent proportion (32.8%) of disagreements between diagnosis of the Registry and cause of death reported on death certificate was observed, concerning errors of the second and third digit of ICD-9 (21.9%) and for lack of mention of cancer in the death certificate. The main causes of the loss of information were the issuing of the certificate by a M.D. of the permanent medical ward and not by the family doctor, and the lack of the document released by the hospital upon discharge of the patient, usually containing indication on diagnosis and treatment.