Littre's Umbilical Hernia in a Child: A Case Report and Scoping Review.

Littre's umbilical hernia (UH) is a rare disease, the third most common Littre hernia. Most case reports interest adult patients. We reported the case of a four-year-old girl with anemia and symptomatic UH, with an incidentally diagnosed Meckel's diverticulum (MD) containing pancreatic ectopic tissue. We reviewed case reports on Littre's umbilical hernia without a date or language restriction. Including our patient, 21 cases were reviewed, of whom 15 (71.4%) were adults and 13 (61.9%) were males. Complicated umbilical hernia occurred in 13 patients (61.9%) and symptomatic MD in two children (9.5%). Investigations preoperatively diagnosed two patients (9.5%). Eighteen patients (85.7%) underwent open surgery, Meckel's diverticulum removal was performed in 18 patients (85.7%), and primary umbilical hernia repair was performed in 16 (76.2%). Ectopic tissue was present in four patients (19.1%), and long-term outcomes were excellent in all patients.

Changes in admissions, and hospitalization outcomes of IBD patients in an Italian tertiary referral center over a 13-year period.

OBJECTIVE: The management of Inflammatory Bowel Disease (IBD) has changed significantly in recent years, mainly due to the introduction of biologic medications, however, other factors may also have a role. The aim of this study was to evaluate the evolution of IBD admissions, including trends, modality of admission and rates of surgical intervention, in a tertiary care center. PATIENTS AND METHODS: Hospitalization of patients with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were identified between 2000 and 2013, using ICD-9-CM codes for IBD, from our hospital database. The following parameters were evaluated for each admission: type of admission (ordinary vs. day care service), mode of admission (elective vs. emergency care, for ordinary admissions only), admission code, surgical procedures and complication rates. Comparison between pre- and post-biologic therapy introduction years was also performed. RESULTS: Between 2000 and 2013 a total of 8834 IBD-related admissions were recorded. Hospitalizations increased linearly reaching a peak in 2006, with a downward trend in the following years. The downward trend was especially marked for patients younger than 40 years. No significant differences in hospitalization trends between CD and UC were recorded. Disease flare represented the cause of hospitalization in approximately 50% of cases. Overall, 10.8% of patients underwent surgery with no difference between the two conditions. Complications occurred in 28.7% of admissions. CONCLUSIONS: Hospitalizations for IBD patients have decreased in recent years, especially in younger patients. However, a significant proportion of patients are still admitted to complete diagnostic workup, indicating the need to better implement outpatient services. A clear reduction in surgery occurrence over time could not be observed in our study.

Metabolic rejuvenation upgrades circulatory functions of red blood cells stored under blood bank conditions.

BACKGROUND: Red blood cells (RBC) change upon hypothermic conservation, and storage for 6 weeks is associated with the short-term clearance of 15% to 20% of transfused RBCs. Metabolic rejuvenation applied to RBCs before transfusion replenishes energetic sources and reverses most storage-related alterations, but how it impacts RBC circulatory functions has not been fully elucidated. STUDY DESIGN AND METHODS: Six RBC units stored under blood bank conditions were analyzed weekly for 6 weeks and rejuvenated on Day 42 with an adenine-inosine-rich solution. Impact of storage and rejuvenation on adenosine triphosphate (ATP) levels, morphology, accumulation of storage-induced microerythrocytes (SMEs), elongation under an osmotic gradient (by LORRCA), hemolysis, and phosphatidylserine (PS) exposure was evaluated. The impact of rejuvenation on filterability and adhesive properties of stored RBCs was also assessed. RESULTS: Rejuvenation of RBCs restored intracellular ATP to almost normal levels and decreased the PS exposure from 2.78% to 0.41%. Upon rejuvenation, the proportion of SME dropped from 28.2% to 9.5%, while the proportion of normal-shaped RBCs (discocytes and echinocytes 1) increased from 47.7% to 67.1%. In LORCCA experiments, rejuvenation did not modify the capacity of RBCs to elongate and induced a reduction in cell volume. In functional tests, rejuvenation increased RBC filterability in a biomimetic splenic filter (+16%) and prevented their adhesion to endothelial cells (-87%). CONCLUSION: Rejuvenation reduces the proportion of morphologically altered and adhesive RBCs that accumulate during storage. Along with the improvement in their filterability, these data show that rejuvenation improves RBC properties related to their capacity to persist in circulation after transfusion.

SARS-CoV2 RNA detection in a pancreatic pseudocyst sample.

The involvement of gastrointestinal system in SARS-CoV2 related disease, COVID-19, is increasingly recognized. COVID-19 associated pancreatic injury has been suggested, but its correlation with pancreatic disease is still unclear. In this case report, we describe the detection of SARS-CoV2 RNA in a pancreatic pseudocyst fluid sample collected from a patient with SARS-CoV2 associated pneumonia and a pancreatic pseudocyst developed as a complication of an acute edematous pancreatitis. The detection of SARS-CoV2 within the pancreatic collection arise the question of whether this virus has a tropism for pancreatic tissue and whether it plays a role in pancreatic diseases occurrence.

Gut Microbiota: A Key Modulator of Intestinal Healing in Inflammatory Bowel Disease.

Mucosal healing (MH) represents a crucial factor for maintaining gut homeostasis. Indeed, in inflammatory bowel disease, MH has become the standard therapeutical target, because it is associated with more effective disease control, more frequent steroid-free remission, lower rates of hospitalization and surgery, and improved quality of life. In this scenario, gut microbiota is a crucial player in modulating intestinal repair and regeneration process. It can act on the tumor necrosis factor-α production, modulation of reactive oxygen and nitrogen species, activity of matrix metalloproteinases and on many other mechanisms strictly involved in restoring gut health. In this review, we analyze and review the literature on the role of gut microbiota in sustaining mucosal injury and achieving MH.

Paradoxical psoriasis in a large cohort of patients with inflammatory bowel disease receiving treatment with anti-TNF alpha: 5-year follow-up study.

BACKGROUND: Psoriasis is an emerging paradoxical side effect in patients with inflammatory bowel disease (IBD) when treated with anti-TNF alpha. Patients with severe skin lesions unresponsive to topical therapy need to withdraw from treatment. AIM: To estimate the incidence of paradoxical psoriasis in a large cohort of IBD patients treated with anti-TNF alpha and to analyse its clinical correlates. METHODS: A retrospective cohort study on all IBD patients who started anti-TNF alpha at our IBD Centre from January 2008 to December 2013 was performed. Proportional hazards regression models were used to estimate the association between each predictor and time to the development of psoriasis. Time-dependent predictors were updated at each available time point. RESULTS: Four hundred and two patients were included. Participants contributed a total of 839 person-years of follow-up, during which 42 incident cases of psoriasis were recorded, with an incidence rate of five per 100 person-years. Cox-regression survival analysis revealed smoking as independent predictor of psoriasis (HR: 2.37, 95% CI: 1.36-4.48; P = 0.008). Conversely, concomitant immunosuppressive therapy was inversely related to psoriasis (HR: 0.33, 95% CI: 0.12-0.92; P = 0.03). CONCLUSIONS: Paradoxical psoriasis is a relevant side effect of anti-TNF alpha therapy, with an incidence rate of five per 100 person-years. Smoking is confirmed as the main risk factor for developing lesions. The combination therapy with anti-TNF alpha plus immunosuppressants is associated with a reduced risk of paradoxical psoriasis.

Fertility drugs and breast cancer risk.

PURPOSE OF INVESTIGATION: Female infertility is a widespread problem in Western countries. During past years, an association between ovarian stimulation in unfertile women and breast cancer risk has been hypothesized. OBJECTIVE: Purpose of the present investigation was to comment the most updated studies about an eventual relationship between fertility drugs and breast cancer risk. MATERIALS AND METHODS: The authors performed a review of the current literature regarding the possible association between the use of fertility drugs and the enhanced risk of breast cancer. They searched digital databases including Pubmed, EMBASE, and the Cochrane Library. The literature search was performed using various combinations of keywords. They carefully analyzed only the full versions of all relevant studies. RESULTS: Using various combination of keywords, the authors examined 930 papers. They considered only papers written in English. With these criteria they selected the studies that had been discussed in detail on the text. CONCLUSION: None of the works commented provides an indisputable evidence about a link between ovarian stimulation and breast cancer risk. On the contrary, most of them actually suggest a lack of interaction between them or even a protective role of ovarian stimulation.

From conventional chemotherapy to targeted therapy: use of monoclonal antibodies (moAbs) in gastrointestinal (GI) tumors.

In recent years, significant progress has been made in the diagnosis and treatment of gastrointestinal cancers. Researches and clinicians however are still faced with challenges, not the least is the detection and management of tumors with varied gene mutation status. Clarification of the molecular pathology of gastrointestinal cancers may improve treatment options as well as quality of life and the long-term survival of this patient class. Therefore, molecular-targeted therapies have emerged as clinically useful drugs for gastrointestinal cancers cure, and predictive biomarkers have been heralded as the way to develop the right drug for the right patient. Moving from such appealing molecular background, we wrote an overview of the main targeted therapies, with particular interest to monoclonal antibodies that have already been approved in clinical practice or are being tested in gastrointestinal cancers treatment.

Respiratory syncytial virus infection in hospitalized children older than 2 years with community-acquired pneumonia.

BACKGROUND/AIM: Respiratory syncytial virus (RSV) is one of the main causes of bronchiolitis and pneumonia in infants and young children. The aims of the present study were to evaluate the role of RSV in children >2 years old hospitalized with community-acquired pneumonia (CAP) and to type the circulating RSV strains. MATERIALS AND METHODS: Serum and throat swab samples were taken upon admission from Greek children aged > 2 years, hospitalized with atypical CAP, and when possible, a second serum sample was also taken. RSV IgG and IgM antibodies were determined by Enzyme Linked Immunosorbent Assay (ELISA), while throat swab samples were tested by nested RT-PCR. Additional serological testing was performed to find out probable co-infections. RESULTS: A total of 101 children with atypical CAP were included in the study, aged 2.5-14 years (median 8.25). RSV IgM antibodies were detected in 21 (20.7%) cases, either in the first or/and in the second serum sample, while RSV genome was detected in 11 out of 15 (73%) IgM-positive patients, which were further tested by PCR. PCR-positive results were obtained up to the 7(th) day of illness. Among the 11 cases, one was of type B, and all the rest were of type A. The median age of the RSV-positive children was 4 years (range 3-13 years). Although RSV was detected in all seasons, the majority of cases (31%) were detected in winter. Co-infection was detected in 3 cases (two with Mycoplasma pneumoniae and one with adenovirus). CONCLUSIONS: Apart from the known role of RSV as the most important pathogen causing acute respiratory disease in infants and young children, it is also a significant viral pathogen in older children hospitalized because of CAP. Genetic typing provides further insight into the epidemiology of the disease.

Development of psoriasis scalp with alopecia during treatment of Crohn's disease with infliximab and rapid response to both diseases to ustekinumab.

Anti tumor necrosis factor antibodies are used to treat both psoriasis and inflammatory bowel disease. Several paradoxical cases of psoriatic skin lesions induced by tumor necrosis factor antagonist therapy have been described in IBD patients in the recent years. Ustekinumab, a fully human anti-interleukin-12/-23 monoclonal antibody, is the first drug of a new class of biologic therapy approved for the treatment of moderate to severe plaque psoriasis. Data on the efficacy of ustekinumab in patients with moderate-to-severe Crohn's disease, especially in patients previously treated with infliximab, have been recently published. We report about the effectiveness of ustekinumab in the treatment of both severe scalp psoriasis lesions with alopecia and active Crohn's disease.

The radiosensitization effect of titanate nanotubes as a new tool in radiation therapy for glioblastoma: a proof-of-concept.

BACKGROUND AND PURPOSE: One of the new challenges to improve radiotherapy is to increase the ionizing effect by using nanoparticles. The interest of titanate nanotubes (TiONts) associated with radiotherapy was evaluated in two human glioblastoma cell lines (SNB-19 and U87MG). MATERIALS AND METHODS: Titanate nanotubes were synthetized by the hydrothermal treatment of titanium dioxide powder in a strongly basic NaOH solution. The cytotoxicity of TiONts was evaluated on SNB-19 and U87MG cell lines by cell proliferation assay. The internalization of TiONts was studied using Transmission Electron Microscopy (TEM). Finally, the effect of TiONts on cell radiosensitivity was evaluated using clonogenic assay. Cell cycle distribution was evaluated by flow cytometry after DNA labeling. DNA double-stranded breaks were evaluated using γH2AX labeling. RESULTS: Cells internalized TiONts through the possible combination of endocytosis and diffusion with no cytotoxicity. Clonogenic assays showed that cell lines incubated with TiONts were radiosensitized with a decrease in the SF2 parameter for both SNB-19 and U87MG cells. TiONts decreased DNA repair efficiency after irradiation and amplified G2/M cell-cycle arrest. CONCLUSION: Our results indicated that further development of TiONts might provide a new useful tool for research and clinical therapy in the field of oncology.

A case of pyoderma gangrenosum with ulcerative colitis treated with combined approach: infliximab and surgery.

Pyoderma gangrenosum (PG) is an ulcerating noninfectious disease of the skin seen in 1-2% of patients with inflammatory bowel disease (IBD). The pathogenesis of PG has yet to be determined, but may be related to abnormal T cell responses and the production of TNF-α, a pathway also involved in IBD pathogenesis. Infliximab, a chimeric monoclonal antibody to TNF-α, is used to treat moderate to severe IBD and several case reports and studies suggest the efficacy of infliximab in the treatment of PG. The surgical approach to PG is reserved to a few selected cases. We report here the case of a patient with ulcerative colitis (UC) and PG localized on the left breast, treated with a simultaneous combined medical and surgical approach.

Immune response to influenza A/H1N1 vaccine in inflammatory bowel disease patients treated with anti TNF-α agents: effects of combined therapy with immunosuppressants.

BACKGROUND AND AIMS: Our first objective was to evaluate the immune response to the adjuvanted 2009 A/H1N1 pandemic (pH1N1) vaccine in inflammatory bowel disease (IBD) patients treated with anti-TNF-α alone or combined with immunosuppressants (IS). Second and third aims were the safety of pH1N1 vaccine and the effects on IBD clinical activity. METHODS: 36 patients with Crohn's disease (CD) and 26 with ulcerative colitis (UC) and thirty-one healthy control (HC) subjects were enrolled. 47 patients were on anti TNF-α maintenance monotherapy and 15 on anti TNF-α combined with IS. Sera were collected at baseline (T0) and 4 weeks after the vaccination (T1) for antibody determination by hemagglutination inhibition (HAI). Disease activity was monitored at T0 and T1. RESULTS: Seroprotective titers (≥1:40) in patients were comparable to HC. Seroconvertion rate (≥4 fold increase in HAI titer) was lower than HC in IBD patients (p=0.009), either on anti TNF-α monotherapy (p=0.034) or combined with IS (p=0.011). Geometric mean titer (GMT) of antibodies at T1 was significantly lower in patients on combined therapy versus those on monotherapy (p=0.0017) and versus HC (p=0.011). The factor increase of GMT at T1 versus T0 was significantly lower in IBD patients versus HC (p=0.042), and in those on combined immunosuppression, both versus monotherapy (p=0.0048) and HC (p=0.0015). None of the patients experienced a disease flare. CONCLUSION: Our study has shown a suboptimal response to pH1N1 vaccine in IBD patients on therapy with anti TNF-α and IS compared to those on anti-TNF-α monotherapy and HC.

Anti-TNF alpha therapy in the management of extraintestinal manifestation of inflammatory bowel disease.

Inflammatory bowel disease, Crohn's disease and ulcerative colitis, are immune-mediated disorders of unknown etiology that primarily affect the gastrointestinal tract. In addition, other organ systems can be involved such as joint/bones, skin, eyes, hepatobiliary tract, lungs and kidney. Overall, they represent extraintestinal manifestations of inflammatory bowel disease and may present before, in conjunction or after the onset of bowel disease. Extraintestinal manifestations are observed in 20-40% of patients and frequently have a negative impact on quality of patients' life. Some extraintestinal manifestations such as arthritis, erytema nodosum, pyoderma gangrenosum, iritis, uveitis have a pathogenic tumor necrosis factor alpha-dependent mechanism common with Crohn's disease and ulcerative colitis. Early recognition and treatment of extraintestinal manifestations can minimize potential severe complications. In this review we provide an overview on the prevalence and clinical aspects of the more commonly reported extraintestinal manifestations of Crohn's disease and ulcerative colitis and the role of tumor necrosis factor alpha inhibitors in their treatment.

[Identification and characterization of microRNA involving in malignant pleural mesothelioma]. / Identificazione e caratterizzazione dei microRNA coinvolti nel mesotelioma pleurico maligno.

One of the research areas of modern medicine is to work on the identification of biological markers, such as biomolecular ones, for neoplastic diseases from occupational origin. MiRNA, short RNA no-codifing sequences, are recently identified such as diagnostic markers in several type of cancer. For this reason, the aim of our study is to analyze the possible role of miRNA in malignant pleural mesothelioma, a rare and aggressive tumor with a strong resistance to conventional therapies and poor prognosis. Total RNA, containing also miRNA, was extracted, and RNA was retro-transcripted with specific primers. Then, miRNA expression was tested using real-time PCR method and particular probes for each miRNA. The RNU6B was used such as housekeeping gene, for data normalization. This work represents the first step for the identification of a specific miRNA pattern for MPM, which will be useful in the diagnosis of MPM and for a personalized therapeutic treatment.

New biological agents for the treatment of the "high risk" IBD patients.

BACKGROUND: Several new biological drugs have been introduced in the last decade or are under investigation for the treatment of IBD. They include anti TNFalpha agents, anti adhesion molecules, anti IL-12/23, anti IL-6R and others. Their role in IBD therapy will be discussed in regard of the association of chronic inflammation and cancer in the gut. The risk of colorectal cancer is increased in ulcerative colitis (UC) and, to some extent, in Crohn's disease (CD). This association is well known from many years. However, the mechanisms linking chronic inflammation and carcinogenesis are beginning to be elucidated only recently. RESULTS AND CONCLUSIONS: Experimental data indicate that several cytokines could play a role in promoting tumour development. In this perspective, the anti cytokine agents could be not only powerful tools in treating inflammation but also efficacious in preventing the onset of inflammation associated colorectal cancer.

Fatal Mediterranean spotted fever in Greece.

Forty-five days after the first confirmed and fatal Crimean-Congo haemorrhagic fever (CCHF) case in Greece in 2008, a female patient with similar signs and symptoms (high fever, thrombocytopaenia) and resident of the same area, was admitted to the University General Hospital of Alexandroupolis. Before admission, she had visited a local hospital where a cephalosporin was prescribed. A rash manifested over subsequent days, which was misdiagnosed as an allergy to the drug. Upon admission to the University Hospital, she was given further antibiotics, including doxycycline; a few hours later, ribavirin was added because CCHF was suspected. After the patient's death, rickettsiosis caused by Rickettsia conorii conorii (Meditteranean spotted fever; MSF) was diagnosed. Extremely high values of interleukin (IL)-1ra, IL-6, interferon-gamma-inducible protein-10, monocyte chemoattractant protein-1 and an absence of tumour necrosis factor-alpha were observed. MSF is a potentially severe and even fatal disease resembling viral haemorrhagic fevers that has to be included in the differential diagnosis of febrile syndromes combined with thrombocytopaenia, even when a tick bite is not reported, and an eschar is absent. Physicians have to be aware of MSF in patients with severe disease who are returning from the Mediterranean area.

New therapeutic approach in inflammatory bowel disease.

In the last decade, biologic agents, in particular infliximab and adalimum-ab, have deeply changed the therapeutic armamentarium of inflammatory bowel disease (IBD). However, these drugs have a number of contraindications and side-effects that physicians should know so to avoid and eventually manage them. Another important issue is the early introduction of immunomodulators and biologics in the therapeutic algorithm of IBD, the so called "top-down" approach compared to the traditional "step-up" approach. In this review, the indications to the use of anti-TNF-alpha molecules in IBD are briefly reported and the potential benefits and disadvantages of a more aggressive approach are discussed.

Regulation of apoptosis by PML and the PML-NBs.

The promyelocytic leukemia protein (PML) is a tumor suppressor identified in acute PML and implicated in the pathogenesis of a variety of tumors. PML is essential for the proper assembly of a nuclear macromolecular structure called the PML nuclear body (PML-NB). PML and PML-NBs are functionally promiscuous and have been associated with the regulation of several cellular functions. Above all these is the control of apoptosis, a function of PML whose physiological relevance is emphasized by in vivo studies that demonstrate that mice and cells lacking Pml are resistant to a vast variety of apoptotic stimuli. The function of PML in regulating apoptosis is not confined to a linear pathway; rather, PML works within a regulatory network that finely tunes various apoptotic pathways, depending on the cellular context and the apoptotic stimulus. Here, we will summarize earlier and recent advances on the molecular mechanisms by which PML regulates apoptosis and the implication of these findings for cancer pathogenesis.