Alcohol-related Liver Disease and sepsis.

OBJECTIVE: Sepsis is one of the most common complications and causes of death in patients with Alcohol-related Liver Disease. This narrative review will focus on several aspects of sepsis in the context of Alcohol-related Liver Disease. The pathophysiology of the increased susceptibility to infections consists mainly of impaired innate and adaptive immunity, changes in gut microbiota with consequent gut translocation of bacteria due to both alcohol abuse and the underlying liver disease. The diagnosis of sepsis in the context of Alcohol-related Liver Disease is challenging. Moreover, the use of classical acute-phase serum proteins (e.g., C-reactive protein and procalcitonin) has several limitations in this setting. The early administration of an adequate antibiotic treatment is pivotal. Finally, measures of infection control and prevention are needed because the prognosis of sepsis in patients affected by Alcohol-related Liver Disease is poor.

Non-Occlusive Mesenteric Ischemia (NOMI) in Parkinson's disease: case report.

Non-occlusive mesenteric ischemia (NOMI) is a severe pathological condition characterized by signs and symptoms of bowel obstruction, intestinal necrosis resulting from acute and/or chronic inadequate blood perfusion, in the absence of an organic vascular obstruction detectable by imaging techniques. A 64 years old man case with a history of Parkinson's disease in high-functioning levodopa treatment is presented. Clinical and radiological signs of intestinal obstruction were observed. He underwent surgical operation with total colectomy and terminal ileostomy for generalized secondary peritonitis due to perforation of sigmoid colon. Ischemic pancolitis was first suspected. In third post-operative day a contrastenhanced CT scan was performed in the evidence of fever and sub-occlusive symptoms. It was found absence of reliable evidence of vascular changes; superior mesenteric artery and vein patency is maintained A NOMI was then diagnosed. NOMI represents about 0.04% of mesenteric artery diseases. It is correlated with a poor prognosis with a mortality estimated of 70-90%. Parkinson's disease, considering neurodegenerative alterations that characterize it, can be considered as a predisposing factor. The combined treatment with high doses of levodopa and vasodilators, such as PGE (Prostaglandin E), can contribute to an improvement in prognosis.

23-hour observation endocrine neck surgery: lessons learned from a case series of over 1700 patients.

Although the surgical procedures concerning the thyroid and the parathyroid glands are considered safe, the possible occurrence of complications (mainly hematoma and hypocalcemia) limit the short stay surgery. At our institution a 23-hour-surgery with overnight hospital stay for endocrine neck surgical procedures was introduced since 2004. The present case series analyses the institutional results. Over 1913 endocrine neck surgery procedures, 1730 patients (90,2%) were managed according to this model. Among these patients, 92 suffered from hypocalcemia, 12 from airways obstruction due to the hematoma, 5 from bilateral nerve palsy. 15 more patients had unpredictable general disease compromising the short-stay surgery management. The goal of the discharge after 23 hours was achieved in 92,8% of cases with a mean hospital stay of 1,1days. The 23-hour observation with an overnight surgery is feasible and safe if the correct indications are observed. A considerable volume of specific activity is needed.

Deep SSI after mesh-mediated groin hernia repair: management and outcome in an Emergency Surgery Department.

AIM: Mesh-mediated groin hernia repair is considered the goldstandard procedure. It has low recurrence rate. Rarely a deep Surgical Site Infection (SSI) is seen when a synthetic prosthesis is used. CASE REPORT: We describe a rare case of bilateral deep SSI after mesh-mediated groin hernia repair. Diagnosis was performed through the physical examination and radiological exams. Microbiological samples identified a methicillin-resistant Staphylococcus aureus responsible of the infection. Target therapy was performed and re-operation performed in order to remove the infected prosthesis and to apply a biological one to create the fibrous scaffold. During follow-up time, right side recurrence was observed. Tru-cut biopsy of fascia was obtained in order to identify the responsible of the recurrence. CONCLUSION: Combination of antibiotic therapy and surgical reoperation seems to be the correct way to approach the deep SSI after mesh-mediated groin hernia repair. The use of biological mesh after synthetic removal seems to improve the final outcome.

Acute appendicitis: should the laparoscopic approach be proposed as the gold standard? Six-year experience in an Emergency Surgery Unit.

Acute appendicitis is common in an Emergency Surgery Unit. Although the laparoscopic approach is a method accepted for its treatment, no strong data are available for determining how many procedures must an experienced surgeon carry out for obtaining all the advantages of this technique and if this approach can become the gold standard in the activity of a general emergency unit with senior surgeons variously skilled on the basic laparoscopy. 142 patients that underwent appendectomy (90 laparoscopic, 52 conventional) for acute appendicitis were enrolled in this institutional retrospective cohort study. The surgeons were classified with a descriptor-based grading and divided in two groups regarding the skill. The only relevant result of our study was the significant reduction of conversion rate in case of laparoscopic approach. No strong differences were found concerning the duration of the procedure and the hospital stay between the two groups. The rate of complications were very low in both groups. In conclusion, the experienced surgeons can easily perform a laparoscopic approach independently from the specific skill in this approach.

Risk factors for hypoglycemia in patients with type 2 diabetes, hospitalized in internal medicine wards: Findings from the FADOI-DIAMOND study.

AIMS: Hypoglycemia is a potential risk in the management of patients suffering from type 2 diabetes (T2DM) and hospitalized in internal medicine units (IMUs). The aim of this analysis was to evaluate incidence of hypoglycemia and related risk factors in a group of patients admitted to IMUs. METHODS: We used the FADOI-DIAMOND study carried out in 53 Italian IMUs. The DIAMOND design included two cross-sectional surveys interspersed with an educational program. In both phases each center reviewed the charts of the last 30 hospitalized patients with known T2DM (n=3167), including information about hypoglycemia during hospital stay. The association between occurrence of hypoglycemia and potential predictors was evaluated by means of a multivariable logistic regression analysis. RESULTS: A total of 385 symptomatic hypoglycemic events were observed (rate=12%). Advanced age, cognitive dysfunction, and nephropathy were associated with hypoglycemia. Hypoglycemia occurred in 19.4% of patients treated according to the insulin sliding-scale method versus 11.4% of patients treated with basal bolus (p<0.01). More patients with hypoglycemia received sulfonylureas versus the no-hypoglycemia group (28.3% versus 20.6%, p<0.001). Significantly longer length of hospital stay and increased in-hospital mortality were found in the group with hypoglycemia compared with the no-hypoglycemia group (12.7±10.9 versus 9.6±6.5 days; 8.8% versus 4.8%, p<0.01). CONCLUSIONS: Hypoglycemia in hospitalized patients with diabetes is associated with increased length of hospitalization and in-hospital mortality. Identification of patients at increased risk of hypoglycemia may be important for optimally adapting treatment and patient management.

NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance.

Sorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 significantly increased cell sensitivity to sorafenib and inhibited the cell growth, migration and invasion of HCC cells, both in vitro and in vivo. Moreover, NUPR1 silencing influenced the expression of RELB and IER3 genes. Unsurprisingly, RELB and IER3 knockdown also inhibited HCC cell viability, growth and migration. Using gene expression profiling of HCC cells following stable NUPR1 knockdown, we found that genes functionally involved in cell death and survival, cellular response to therapies, lipid metabolism, cell growth and proliferation, molecular transport and cellular movement were mostly suppressed. Network analysis of dynamic gene expression identified NF-κB and ERK as downregulated gene nodes, and several HCC-related oncogenes were also suppressed. We identified Runt-related transcription factor 2 (RUNX2) gene as a NUPR1-regulated gene and demonstrated that RUNX2 gene silencing inhibits HCC cell viability, growth, migration and increased cell sensitivity to sorafenib. We propose that the NUPR1/RELB/IER3/RUNX2 pathway has a pivotal role in hepatocarcinogenesis. The identification of the NUPR1/RELB/IER3/RUNX2 pathway as a potential therapeutic target may contribute to the development of new treatment strategies for HCC management.

Mannheim Peritonitis Index (MPI) and elderly population: prognostic evaluation in acute secondary peritonitis.

INTRODUCTION: Acute Secondary Peritonitis due to abdominal visceral perforation is characterized by high mortality and morbidity risk. Risk stratification allows prognosis prediction to adopt the best surgical treatment and clinical care support therapy. In Western countries elderly people represent a significant percentage of population Aim. Evaluation of Mannheim Peritonitis Index (MPI) and consideration upon old people. PATIENTS AND METHODS: Retrospective study on 104 patients admitted and operated for "Acute Secondary Peritonitis due to visceral perforation". MPI was scored. In our study we want to demonstrate efficacy of MPI and the possibility to consider older age an independent prognostic factor. RESULTS: Mortality was 25.96%. Greatest sensitivity and specificity for the MPI score as a predictor of mortality was at the score of 20. MPI score of <16 had 0.15 times lower risk of mortality compared to patients with MPI score 17 - 21 and 0.61 lower than patients with MPI >22. Patients with MPI score 17-21 had 0.46 times lower risk of mortality compared to patients with MPI score >21. In the group of patients with MPI score of >20 the mortality rate was 48.5% for patients older than 80 years old and 12.1% for younger patients (p < 0.005); in the group with MPI score of < 20 mortality rate was respectively 8.4% and 1.4% (p < 0.005). DISCUSSION AND CONCLUSIONS: Data confirm the accuracy of the test. MPI score and age over 80 years old resulted independent predictors of mortality at multivariate analysis.

Heart rate behavior during an exercise stress test in obese patients.

BACKGROUND AND AIMS: Heart rate (HR) response to exercise has not been fully described in the obese. We wanted to study the differences between obese and non-obese patients in HR behavior during an exercise stress test and to determine whether these differences influence exercise capacity. METHODS AND RESULTS: We studied 554 patients (318 females) who underwent a treadmill exercise test. All subjects were in sinus rhythm. Patients with ischemic heart disease, with reduced ejection fraction and patients taking drugs that interfere with HR were excluded. The population included 231 patients with BMI<30 kg/m(2) (group 1), 212 patients who were unfit and obese (group 2) and 111 patients who were trained obese (group 3). Resting HR was similar in the various groups. Peak HR, HR recovery and chronotropic index were lower in obese subjects, regardless of their fitness level. Multivariate analysis showed that HR related variables were associated with age, BMI, height, hypertension and various pharmacologic treatments, while exercise capacity was strongly dependent on HR behavior, as well as on sex, age, BMI and diabetes. CONCLUSION: Obese subjects have a marked impairment of HR behavior during exercise and in the recovery period, and the blunted increase in HR is the most important factor that influences exercise capacity.

Prevalence of oedema of the lower limbs in multiple sclerosis patients: a vascular and lymphoscintigraphic study.

The aim of the study was to evaluate the frequency of oedema of the lower limbs in multiple sclerosis (MS) patients utilizing a multidisciplinary approach. A total of 205 patients with definite MS were included in the study. Seventy-five were male and 130 female, with a mean age of 50.53, mean Expanded Disability Status Scale (EDSS) score of 5.27 and mean disease duration of 16.6 years. Seventy-one patients had a relapsing-remitting (RR) disease course, 85 were secondary progressive (SP) and 49 were primary progressive (PP). Ninety-three patients (45%) showed oedema at the examination. EDSS, disease duration and disease course, but not gender, were statistically different between oedema and non-oedema patients. Out of 93 patients with oedema, 69 agreed to undergo a vascular examination. Of 69 patients, 45 (65.2%) had a CEAP score (specific rating scale for oedema) of 3 (presence of oedema) and 24 (34.8%) had a score of 4 (presence of a trophic disorder). Out of 69 subjects, 33 agreed to undergo a lymphoscintigraphy, which was normal in only 29 extremities out of 66. Lower limb oedema is common in MS patients, especially in those with reduced mobility. Early screening is advised in patients with an elevated EDSS.

Novel splicing and missense mutations in autosomal dominant polycystic kidney disease 1 (PKD1) gene: expression of mutated genes.

Autosomal dominant polycystic kidney disease (ADPKD) is a common disorder mostly characterized by cyst formation in kidney tubules. The majority of ADPKD cases is caused by mutations in the PKD1 gene, but no prevalent mutation has been reported. By heteroduplex analysis of the 3' single-copy region of the gene, we have searched for mutations in subjects from 40 ADPKD families of Northern Italy. Seven novel polymorphisms and three novel disease-associated mutations (R3718Q, L3851P and IVS45+56del25) were identified. Both missense mutations are located in the major extracellular loop of polycystin-1. The 25 bp deletion inside intron 45 did not affect 5' and 3' consensus splicing sites, but caused a 56 nucleotide out of frame-deletion due to activation of a cryptic 3' splice site in exon 46. The mutated RNA should produce a truncated polycystin 1 at the G binding peptide in the intracellular C-terminal end of the protein. RT-PCR analysis showed that the disease-associated mutations were present in transcribed sequences. In particular, RNA analysis of BHK cells transfected with PKD1 genomic DNA, including the deleted intron, showed that no normal transcript is produced by the deleted gene. This intronic mutation, found in a large pedigree, seems to be associated with a prevalence of cerebrovascular disease.

Mutations in autosomal dominant polycystic kidney disease 2 gene: Reduced expression of PKD2 protein in lymphoblastoid cells.

The polycystic kidney disease 2 (PKD2) gene, encoding a 968-amino acid integral membrane protein with six predicted membrane-spanning domains and intracellular NH2 and COOH termini, is mutated in approximately 15% of the cases of autosomal dominant polycystic kidney disease (ADPKD), a common genetic disease frequently resulting in renal failure. For a better understanding of the cause of this disorder, we searched for mutations in the PKD2 gene in two PKD2-linked families characterized by different clinical phenotypes. A common polymorphism, a nonsense mutation, and a frameshift mutation were found. Both mutations are predicted to produce truncated proteins of 314 and 386 amino acids, arrested at the first extracellular loop of the protein. Restriction enzyme analysis of polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR products, respectively, showed that mutations cosegregated with the disease and mutated alleles were expressed at the messenger RNA level in lymphoblastoid cell lines. However, in these cells, Western blot analysis showed only PKD2 normal protein, and it was expressed at a lower level than that found in cells without the PKD2 mutation. These findings suggest that in lymphoblastoid cells, the truncated protein product of the mutant allele may not be stable.

K562 erythroid and HL60 macrophage differentiation downregulates polycystin, a large membrane-associated protein.

Polycystin, the PKD1 gene product mutated in autosomal dominant polycystic kidney disease, is a large membrane protein which is important in the differentiation of epithelial tubular structure. Furthermore, PKD1 mRNA is expressed in various tissues and in neoplastic cell lines particularly, suggesting that polycystin might be involved in differentiation and/or proliferation of other cell types. Therefore, in order to investigate such a possible role, polyclonal antibodies against a recombinant polycystin peptide were raised and used to study polycystin expression in human leukemia cell lines committed to differentiation. Using Western blot and laser scanning confocal microscopy analyses, we demonstrated expression of polycystin in erythroleukemia K562 cells as a membrane-associated polypeptide of approximately 450 kDa, mainly localized in cell-cell contacts. Protein size and subcellular distribution were similar to those found in the kidney epithelial KJ29 cell line. In addition, K562 cell erythroid differentiation induced by hemin was characterized by a reduction in polycystin expression, as measured by Western blot and Northern blot analyses. Cytofluorimetric analysis indicated that upon hemin treatment there was a progressive reduction in the number of polycystin-expressing cells as well as in proliferation rate. Furthermore, reduction in proliferating and polycystin-expressing cells was also observed in K562 cells after serum starvation. When serum was added to the serum-deprived cells an increase in cell number as well as in number of polycystin-positive cells was observed. In addition, polycystin, also expressed in promyelocytic leukemia HL60 cells, was downregulated when macrophage differentiation in HL60 was induced by TPA. Therefore, in these leukemic cells downregulation of polycystin appeared to be closely related to reduction in cell proliferation and to induction of differentiation. This suggests that polycystin may play a relevant role in these cell processes.

[Chronic renal insufficiency of single kidney associated with genital, bone, and palpebral malformations]. / Insufficienza renale cronica da rene unico pelvico associato a malformazioni genitali, ossee e palpebrali.

Authors describe renal failure in a young woman with solitary pelvic kidney. Renal malformation was associated with genital and bone malformations that can be accounted for by the close relationship linking the genito-urinary and vertebral apparatuses during the first weeks of intrauterine life. Palpebral malformation which occurs very rarely in cases with renal malformations as reported in the literature was ascribed to hereditary factors. Changes of some indexes (serum and urine electrolytes, plasma renin and aldosterone) observed during the evolution of renal failure appear to confirm the role played by potassium in hormone balance and suggest repeated tests and dietary adjustments.

Craniocerebral gunshot wounds in civilians. Report on 40 cases.

The Authors report an analysis on 40 cases of craniocerebral gunshot wounds treated in a civil hospital over a 8-year period. The important role of CT for a correct diagnosis and treatment planning is stressed even though patients with a G.C.S. lower than 4 die regardless of their CT findings; subdural and intracerebral hematomas are not a serious complication unless patient's neurological status is poor; timing of surgical treatment plays a major role in order to avoid infection of the wound.

Rhizopus arrhizus in Italy as the causative agent of primary cerebral zygomycosis in a drug addict.

A rare case of primary cerebral zygomycosis in an Italian drug addict is described. The diagnosis was based on the histologic detection of broad, aseptate, hyaline mycelium in fluid aspirated from a brain mass detected by computerized axial tomography. The zygomycete isolated from the clinical specimen was identified as Rhizopus arrhizus var arrhizus. The patient had no known predisposing condition that would have suppressed his immunological defenses. Once the diagnosis was established, treatment with amphotericin B was initiated, but the patient died during the first day of treatment.

Computed axial tomography versus NMR for the diagnosis of neurocysticercosis.

A case of generalised neurocysticercosis in a 45-year-old woman is presented with CT and NMR findings. The great additional value of NMR for the diagnosis of this disease is stressed.

Failed lumbar disk syndrome.

The Authors report 8 cases of Failed Lumbar Disk Syndrome (FLDS), on 210 patients operated for slipped disk. Risk factors and the concept that an abnormality involving either neurons in the substantia gelatinosa or internucial fibers in Lissauer's tract is responsible for pain in patients with FLDS are discussed. Since iatrogenic deafferentation pain response to almost all current forms of therapy is generally poor, the most rational approach remains prevention.