Planning Benchmark Study for Stereotactic Body Radiation Therapy of Pancreas Carcinomas with Simultaneously Integrated Boost and Protection: Results of the DEGRO/DGMP Working Group on Stereotactic Radiation Therapy and Radiosurgery.

PURPOSE/OBJECTIVE: The proximity or overlap of PTV and OAR poses a major challenge in SBRT of pancreatic cancer (PACA). This international treatment planning benchmark study investigates whether Simultaneously Integrated Boost (SIB) and Protection (SIP) concepts in PACA SBRT can lead to improved and harmonized plan quality. MATERIALS/METHODS: A multiparametric specification of desired target doses (GTVD50%, GTVD99%, PTVD95%, PTV0.5cc) with two prescription doses of GTVD50%=5×9.2Gy (46Gy) and GTVD50%=8×8.25Gy (66Gy) and OAR limits were distributed with planning CT and contours from 3 PACA patients. In phase 1, plans were ranked using a scoring system for comparison of trade-offs between GTV/PTV and OAR. In phase 2, re-planning was performed for the most challenging case and prescription with dedicated SIB and SIP contours provided for optimization after group discussion. RESULTS: For all 3 cases and both phases combined, 292 plans were generated from 42 institutions in 5 countries using commonly available treatment planning systems. The GTVD50% prescription was performed by only 76% and 74% of planners within 2% for 5 and 8 fractions, respectively. The GTVD99% goal was mostly reached, while the balance between OAR and target dose showed initial SIB/SIP-like optimization strategies in about 50% of plans. For plan ranking, 149 and 217 score penalties were given for 5 and 8 fractions, pointing to improvement possibilities. For phase 2, the GTVD50% prescription was performed by 95% of planners within 2% and GTVD99% as well as OAR doses were better harmonized with notable less score penalties. Fourteen of 19 planners improved their plan rank, 9 of them by at least 2 ranks. CONCLUSION: Dedicated SIB/SIP concepts in combination with multiparametric prescriptions and constraints can lead to overall harmonized and high treatment plan quality for PACA SBRT. Standardized SIB/SIP treatment planning in multicenter clinical trials appears feasible after group consensus and training.

Improvements in one severe progressive multiple sclerosis patient quality of life after an intensity fluid dynamic treatment.

Clinical case: A 49-year-old man (MM72) affected by Secondary Progressive Multiple Sclerosis (SP-MS) since 1998. On last 3 years, neurologists valued 9.0 the patient MM72's EDSS. Methods: MM72 was treated by acoustic waves, modulated in frequency and power by the MAM device, according to an ambulatory intensive protocol. Patient's treatments schedule was organized in thirty cycles of DrenoMAM and AcuMAM, and manual cervical spinal adjustments. Before and after treatments, MSIS-29, Barthel, FIM, EDSS, ESS, and FSS questionnaires were administered to the patient. Results: MM72 patient had improvements in all index score (MSIS-29, Barthel, FIM, EDSS, ESS and FSS) after 30 treatments by MAM plus cervical spine chiropractic adjustments. He showed a significative improvement of his disability and the restore of many functions. After MAM treatments, MM72's cognitive sphere improved of 370%. Fur-thermore, after 5 years of paraplegy, he regained his lower limbs and feet fingers movements with an increase of 230%. Conclusion: We suggest ambulatory intensive treatments by fluid dynamic MAM protocol in SP-MS patients. Statistical analyses are in progress on a larger sample of SP-MS patients.

The connection between diverticulosis and colonic superficial neoplastic lesions in patients who underwent screening colonoscopy.

PURPOSE: If could be a potential pathophysiological connection between colonic diverticula and colonic superficial neoplastic lesions, beyond the shared risk factors, has been a subject of debate in the last years. This study tries to evaluate the association between diverticulosis and colonic neoplastic lesions. METHODS: This is a cross-sectional study including asymptomatic patients who underwent a screening colonoscopy (patients with a positive fecal occult blood test under the regional program of colorectal cancer (CRC) screening), surveillance after polypectomy resection, or familiarity (first-degree relatives) between 2020 and 2021 to evaluate the association between diverticula and colonic polyps. A multivariate analysis with multiple logistic regression and odds ratio (OR) to study the independent association between adenomas and adenocarcinomas was performed. RESULTS: One thousand five hundred one patients were included. A statistically significant association between adenomas or CRC alone and colonic diverticula was found (p = 0.045). On a multivariate analysis of demographic (age, gender) and clinical parameters (familiarity for diverticula and adenoma/CRC), only age was significantly associated with the development of colorectal adenomas or cancer (OR 1.05, 95% CI 1.03-1.07, p < 0.0001). CONCLUSIONS: This study showed a statistically significant association between diverticula and colonic adenomas. However, it is impossible to establish a cause-effect relationship due to the intrinsic characteristics of this study design. A study with a prospective design including both patients with diverticulosis and without colonic diverticula aimed at establishing the incidence of adenoma and CRC could help to answer this relevant clinical question, since a potential association could indicate the need for closer endoscopic surveillance.

A rare case of mycobacterial pseudoaneurysm of the superficial femoral artery.

OBJECTIVE: Extrapulmonary localization of tuberculosis accounts for about 15-20% of cases. Several cases of Mycobacterium tuberculosis with vascular involvement have been described, but only few cases for limb vessels. CASE REPORT: We report the case of a 33-year-old man from Gambia with a symptomatic pseudoaneurysm of the right superficial femoral artery. Total body positron emission tomography/computed tomography with [18F]FDG revealed an active infection. The patient underwent vascular reconstruction with a straight reversed vein graft. Molecular testing for Mycobacterium tuberculosis was non-diagnostic. Cultures of the pseudoaneurysm wall and thrombus removed during surgery grew Mycobacterium tuberculosis. CONCLUSIONS: The diagnosis of vascular tuberculosis infection due to Mycobacterium tuberculosis is a challenge. Epidemiology remains the primary criterion for maintaining a high index of suspicion.

Gallbladder polyps ultrasound: what the sonographer needs to know.

Gallbladder polyps are protuberances of the gallbladder wall projecting into the lumen. They are usually incidentally found during abdominal sonography or diagnosed on histopathology of a surgery specimen, with an estimated prevalence of up to 9.5% of patients. Gallbladder polyps are not mobile and do not demonstrate posterior acoustic shadowing; they may be sessile or pedunculated. Gallbladder polyps may be divided into pseudopolyps and true polyps. Pseudopolyps are benign and include cholesterolosis, cholesterinic polyps, inflammatory polyps, and localised adenomyomatosis. True gallbladder polyps can be benign or malignant. Benign polyps are most commonly adenomas, while malignant polyps are adenocarcinomas and metastases. There are also rare types of benign and malignant true gallbladder polyps, including mesenchymal tumours and lymphomas. Ultrasound is the first-choice imaging method for the diagnosis of gallbladder polyps, representing an indispensable tool for ensuring appropriate management. It enables limitation of secondary level investigations and avoidance of unnecessary cholecystectomies.

Personnel real time dosimetry in interventional radiology.

Interventional radiology and hemodynamic procedures have rapidly grown in number in the past decade, increasing the importance of personnel dosimetry not only for patients but also for medical staff. The optimization of the absorbed dose during operations is one of the goals that fostered the development of real-time dosimetric systems. Indeed, introducing proper procedure optimization, like correlating dose rate measurements with medical staff position inside the operating room, the absorbed dose could be reduced. Real-time dose measurements would greatly facilitate this task through real-time monitoring and automatic data recording. Besides real-time dose monitoring could allow automatic data recording. In this work, we will describe the calibration and validation of a wireless real-time prototype dosimeter based on a new sensor device (CMOS imager). The validation measurement campaign in clinical conditions has demonstrated the prototype capability of measuring dose-rates with a frequency in the range of few Hz, and an uncertainty smaller than 10%.

Hepatitis B virus infection and interferon-inducible protein-10.

Interferon (IFN)-inducible protein-10 (IP-10) is a proinflammatory chemokine, binding the chemokine (C-X-C motif) receptor 3 (CXCR3), which is found mainly on activated T cells and natural killer (NK) cells, and plays an important role in T helper (Th) 1 type inflammatory disorders (autoimmune, neoplastic, and infectious diseases). Concerning viral hepatitis, IP-10 appears to be involved on the pathogenesis of liver damage as well as on the extra-hepatic manifestations either protecting or promoting infection, depending on host immune status and genetic background. During chronic hepatitis B, IP-10 is specifically produced by hepatocytes in inflammatory areas. Here, IP-10 leads to recruitment of T cells, production of IFN-gamma by activated NK T cells, and then monokine induced by IFN-gamma (MIG) and IP-10 secretion by parenchymal and non-parenchymal cells, with a final positive feedback, perpetuating the immune cascade. The increased levels of IP-10 and IP-10 mRNA in the peripheral blood of patients with cirrhosis are closely correlated with the load of HBV DNA in serum, and seem to play a key role in the progression of post-hepatitic cirrhosis. Higher pre-treatment IP-10 levels, and dynamic down-regulation, are associated with an increased probability of hepatitis B e antigen (HBeAg) loss after Peg-IFN therapy. Hepatitis B surface antigen (HBsAg) drop in patients treated with nucleos(t)ide analogues (NAs) is associated with higher baseline IP-10.

Hepatitis C virus and type 1 diabetes.

Hepatitis C virus infection and diabetes mellitus are two worldwide, major public health problems with increasing complication and mortality rates. Type 1 diabetes mellitus (T1D) is characterized by an autoimmune process leading to pancreatic beta cell destruction; only when the major part of pancreatic beta cells have been destroyed the diabetes become clinically manifest. At the basis of the development of the T1D there is an interplay among environmental factors, pancreatic beta cells, the innate and adaptive immune system, the genetic background and the comorbidities of the patient. Viral infections, including hepatitis C virus infection, may be one of the factors that can almost accelerate progression to diabetes, through different mechanisms.

Mixed cryoglobulinemia and thyroid autoimmune disorders.

In patients with hepatitis C virus-associated mixed cryoglobulinemia (MC+HCV) the following thyroid disorders are significantly more frequent than in HCV not infected controls: 1) high levels of serum anti-thyroperoxidase autoantibody (AbTPO), 2) high levels of serum AbTPO and/or anti-thyroglobulin (AbTg) autoantibody; 3) humoral and ultrasonographical signs of thyroid autoimmunity (35%); 4) prevalence of subclinical hypothyroidism (11%). Also, the prevalence of papillary thyroid cancer has been found higher in MC+HCV patients than in controls, in particular in patients with autoimmune thyroiditis. These results suggest a careful monitoring of thyroid function in these patients.

Neurocysticercosis in Europe: Still a public health concern not only for imported cases.

Neurocysticercosis (NCC), a parasitic disease caused by the larvae of the cestode Taenia solium, is the most frequent parasitic disease of the central nervous system (CNS) in the world and the leading cause of secondary epilepsy in Central and South America, East and South Asia, and sub-Saharan Africa. It is endemic in many low- and middle-income countries of the world. Due to increased travels and immigration, NCC may be diagnosed also in non-endemic areas. In fact, tapeworm carriers from endemic zones can transmit infection to other citizens or arrive already suffering NCC. This phenomenon, occurred first in USA during the last 30 years, has been also observed in Europe, as well as in Australia, Canada, Israel, Japan and Muslim countries of the Arab World. Actually, concerning Europe, although, in some areas only few cases have been described, nevertheless the prevalence of NCC may be considered increasing, especially in Spain and Portugal. We reviewed the literature on the burden of NCC in Europe, by a search of PubMed regarding papers from 1970 to present. We only considered on PubMed published and available papers in English, French, Italian, and Spanish, the languages understood by the authors. One hundred seventy six cases of NCC have been reported in seventeen European countries (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Netherlands, Sweden, United Kingdom, and Croatia, Norway, Switzerland). A particular epidemic situation is present in Spain and Portugal. In fact, we collected data that show, in Spain, an increasing incidence both in immigrated patients and in those which were born in certain Spanish geographical areas and, in Portugal, prevalence similar to that observed in endemic areas. Globally, it is clear that as a result of increased migrations and travels from endemic regions, NCC is becoming an emerging public health problem in high-income countries, particularly affecting communities where hygiene conditions are poor and sub-sequentially the parasite can spread from human to human through eggs even in absence of a travel to the tropics. NCC is a preventable disease, it derives that it's important to acquire a great consciousness of the epidemiology and to implement accurate surveillance systems.

A 4-year evaluation of toxoplasmosis seroprevalence in the general population and in women of reproductive age in central Italy.

This study aimed to estimate possible changes in seroprevalence of anti-Toxoplasma gondii IgG and IgM antibodies in people living in the area of Massa and Carrara (central Italy), in recent years. Serum samples from over 13 000 individuals were tested for both IgG and IgM anti- Toxoplasma antibodies using an immunoenzymatic method (Access® Toxo IgG, and Access® Toxo IgM II, Beckman Coulter Inc., USA). Our survey showed a decreasing trend of overall seroprevalence of 24.4% [95% confidence interval (CI) 22.62­25.71] in 2010 compared to 31.0% (95% CI 29.29­32.72) in 2007. A positive trend according to age was found, with low positivity observed in younger age groups. For women of reproductive age the prevalence of IgG antibodies was 30.2% (95% CI 28.44­31.96) in 2007 and 23.6% (95% CI 22.05­25.20) in 2010. IgM seroprevalence in women of this age group also progressively decreased from 1.6% to 0.97% during the study period. Our study confirms a decline of toxoplasmosis in Western countries.

Allelic loss in parathyroid tumors from individuals homozygous for multiple endocrine neoplasia type 1.

Homozygosity for the multiple endocrine neoplasia type 1 (MEN1) gene mutation was described in two of three affected siblings of a kindred in which both parents and the third daughter were heterozygotes. Surprisingly, in the two homozygotes, the disease history did not differ from the one of the heterozygotes. In the attempt to unravel genetic differences in parathyroid tumorigenesis between homozygotes and heterozygotes, restriction fragment length polymorphism analysis and microsatellite PCR analysis for loss of heterozygosity (LOH) at the MEN1 gene region on chromosome 11q13 was performed in parathyroid tissues removed at surgery from the mother, her heterozygous sister, and the three siblings. Allelic losses were evidenced in the larger glands of each patient, with a similar pattern of chromosome 11q12-13 losses. The somatic mutation consisted of a large lose of genetic material from chromosome 11. No gross differences exist in the 11q12-13 LOH observed between homozygous and heterozygous carriers. Interestingly, one of the parathyroid tumors from one heterozygote exhibited region of skipped LOH at the 11q12-13 region. The region in the depth of the critical interval retained heterozygosity, whereas those flanking it shared LOH. These findings indicate that inactivation of both copies of the MEN1 gene are not sufficient for parathyroid tumor development in MEN 1 patients and that tumor suppressor genes, other than the MEN1 gene on chromosome 11 or on other chromosomes, can be involved in the pathogenesis of parathyroid tumorigenesis in MEN 1 syndrome.

Modulation of osteoclast-activating factor activity of multiple myeloma bone marrow cells by different interleukin-1 inhibitors.

We have studied the effects of several interleukin-1 (IL-1) inhibitors--IL-1 receptor antagonist (IL-1ra), soluble IL-1 receptor (sIL-1R) types I and II, and neutralizing monoclonal antibody (mAb) specific for IL-1 receptor type I--on the osteoclast-activating factor (OAF) activity of recombinant IL-1beta and of culture supernatants of unfractionated bone marrow mononuclear cells from multiple myeloma (MM) patients. The latter activity sharply correlated with the IL-1 content of culture supernatants (r = 0.949; p < 0.001). IL-1ra and sIL-1R types I and II had a clear-cut modulating effect on the OAF activity of IL-1beta at saturating doses (2-10 ng/mL); their effect was evident at 2 ng/mL and was dose-dependent over a large range of concentrations. Similarly, the three reagents neutralized the OAF activities of all MM cell supernatants in a dose-dependent fashion and completely abolished them when tested at the fixed concentration of 5 nM. The bone-resorbing activity of tumor necrosis factor-alpha (TNF-alpha) or lymphotoxin (LT), tested alone or added to MM cell supernatants, was affected not at all by IL-1ra and only minimally by sIL-1R types I and II, suggesting that little or no endogenous IL-1 was produced by the rat cells in the assay under TNF-alpha or LT stimulation. Consistent with these findings, PGE2 production elicited by IL-1beta or IL-1-rich supernatants in the rat long-bone assay was abolished by each reagent. Also, mAbs to the IL-1R p80 (type I) chains could modulate the effects of IL-1--recombinant or plasma cell-derived--in the OAF assay, but their activity was markedly less pronounced when compared with the IL-1 inhibitors, since they could never completely abolish bone resorption. Taken together, these findings demonstrate that inhibition of IL-1 interaction with cognate surface receptors on bone cells effectively counteracts its biologic activity. The findings also strongly indicate that OAF activity in conditioned medium of unfractionated myeloma bone marrow cells is predominantly, if not solely, related to IL-1beta.

RFLP analysis of human chromosome 11 region q13 in multiple symmetric lipomatosis and multiple endocrine neoplasia type 1-associated lipomas.

Six lipomas from patients affected by Multiple Symmetric Lipomatosis (MSL) and by Multiple Endocrine Neoplasia Type 1 (MEN 1) were analyzed for loss of heterozygosity on chromosome 11 region q12-13 using four RFLPs. Allelic loss for the D11S146 locus was found only in one visceral MEN 1-associated lipoma. Lipomas that exhibited a lack of allelic lesions were analyzed for an eventual abnormal amount or a defective function of the Gs protein by studying the Gs alpha subunit gene, codons 201 and 207, by PCR and TGGE techniques. All the samples were negative for activating mutations.

Calcium modulates the cyclin D1 expression in a rat parathyroid cell line.

We have used a rat epithelial parathyroid cell line (PT-r) to study the expression and regulation of D-type cyclins. In PT-r cells the cyclin D1 gene is the most abundantly expressed, being transcribed in at least two mRNAs whose levels oscillate during the cell cycle. We also screened a cDNA library prepared from PT-r cells with the human cyclin D1 probe and isolated its rat homologue. Cyclin D2 and D3 mRNAs are both represented in PT-r cells but the former one is only barely detectable. Moreover, the oscillation of cyclin D3 transcript is slightly delayed when compared to cyclin D1 and D2. Since extracellular calcium inhibits parathyroid cell proliferation, we looked for the effect of the ion on the expression of cyclin D genes in PT-r cells. Increasing amounts of calcium in the incubation medium reduced the expression of rat cyclin D1 and D2. The effect appears to be cell-specific and probably mediated through the inhibition of mitogenic signalling pathways.

Aplicacion de criterios diagnostico y valoracion de tratamiento acortado sin Estreptomicina en tuberculosis infantil / Application criteria of diagnosis and validation of shorten treatment without streptomicin in children with tuberculosis

El presente estudio introduce un sistema de diagnostico de tuberculosis infantil en base a criterios epidemiologicos clinicos y radiologicos en pacientes menores de 15 anos, en el departamento de Pediatria del hospital M.I German Urquidi, durante 4 anos, a quienes se les aplico en forma gratuita un tratamiento acortado, triconjugado sin estreptomicina, de 6 meses de duracion con 2 fases de 2 y 4 meses respectivamente. Se logra estudiar a 121 pacientes, mayoritariamente del area rural, desnutridos y en extrema pobreza. El 74 por ciento con alteraciones radiograficas pulmonares u osteoarticulares, el 37 por ciento con diagnostico confirmado por bacteriologia, 67 por ciento con localizacion pulmonar y 13 por ciento con 2 o mas localizaciones clinicas. Se logra curacion en 84 por ciento , fallecieron 6 pacientes y abandonaron 11 por ciento . las complicaciones presentes en 7.4 por ciento relacionadas en su mayoria a intoleranci gastrica.

Interferon-alpha and interleukin 2 synergistically enhance basic fibroblast growth factor synthesis and induce release, promoting endothelial cell growth.

To elucidate mechanisms underlying neovascularization that accompanies certain chronic immune/inflammatory disorders, the effects of interferon-alpha (IFN-alpha) and interleukin 2 (IL-2) on endothelial cell (EC) growth in vitro and angiogenesis in vivo were studied. Preincubation of cultured human ECs with IFN-alpha, followed by exposure to IL-2, resulted in effective stimulation of cell growth, whereas either cytokine alone had only a slight effect. The combination of IFN-alpha/IL-2 induced an angiogenic response in the rabbit cornea. IL-2 receptor expression was enhanced on IFN-alpha-treated ECs: p55 was increased and p70 was induced. 125I-IL-2 binding to ECs treated with IFN-alpha was enhanced (Kd from approximately 7 nM to approximately 260 pM with IFN-alpha), and anti-p55 IgG blocked 125I-IL-2/EC interaction as well as IL-2-mediated EC proliferation. Consistent with these findings in cell culture, immunohistologic studies demonstrated p55 and p70 antigen in the vasculature of rheumatoid joints, but not in normal joint tissue. Exposure of cultured ECs to IFN-alpha increased levels of intracellular EC basic fibroblast growth factor (bFGF), and subsequent addition of IL-2 led to bFGF release into the medium. The observation that anti-bFGF IgG largely blocked EC proliferation in response to IFN-alpha/IL-2 suggested that bFGF was a critical agent in this setting. These data suggest a mechanism rendering ECs responsive to IL-2 which may be relevant in immune/inflammatory disorders: IFN-alpha-mediated induction of functional EC receptors for IL-2, which drives cell proliferation by a mechanism dependent on increased synthesis and release of bFGF.

[Correlation between serum values of copper, ceruloplasmin, SMAO, SDAO, in health- subjects, in pregnant women and in some pathological conditions (author's transl)]. / Relazione tra tassi sierici del rame, della ceruloplasmina, della monoaminossidasi e della diaminossidasi in condizioni normali, in gravidanza ed in alcuni stati morbosi

Copper directly reactive with diethylditiocarbamate, ceruloplasmin, monoamine oxidase (SMAO) and diamine oxidase of the serum (SDAO) were studied in healthy subjects, in nine months pregnant women and in some pathological conditions. Increased values of copper were found in pregnancy. Ceruloplasminaemia was increased in hyperthyroidism, congestive hearth failure, Hodgkin's disease, and in pregnancy. Ceroluplasminaemia was strongly reduced in Wilson's disease. SMAO was increased during pregnancy. Statistical analysis showed no correlations between the variations of the data in different pathological conditions. In healthy subjects and in pregnant women, correlation was found between the values of ceruloplasmin obtained using both enzymatic and KCN methods. Statistical analysis of regression lines obtained in both groups of patients showed significative differences between slopes and elevations. It is possible that ceruloplasmin in pregnant women has different composition compared with healthy controls.