Genotyping of Helicobacter pylori CagA/CagE strains in gastric mucosa and its association with gastric illness.

The aim of this work was associate the presence of the virulence factors of Helicobacter pylori, cagA/cagE, with gastric illness. We found evidence that indicate the contribution of these genotypes with the severity of gastric lesions in patients infected, principally in histological subtypes as atrophic gastritis, and metaplasia.

Megaprosthesis in articular fractures of the lower limbs in fragile patients: a proposal for the therapeutic algorithm.

OBJECTIVE: The use of megaprosthetic implants could provide substantial advantages in elderly population affected by complex fractures. The aim of the study was to identify the patients suitable to megaprosthetic implants in the treatment of lower limbs fractures, as well as periprosthetic fractures. PATIENTS AND METHODS: From January 1st, 2015, to December 31st, 2021, all patients affected by femoral fractures with severe bone loss or previous surgery failure were retrospectively reviewed. ADL, IADL, SF-12 values pre- and post-operative were recorded. Hemoglobin value, NLR, PLR were recorded pre- and peri-operatively for all patients. Complications were recorded. All patients underwent a radiological follow-up. Significance was set at p ≤ 0.05. RESULTS: 23 patients were considered eligible, 10 males and 13 females; the mean age was 72.87 years old (± 12.33), while the mean BMI was 27.2 points (± 5.2). The mean follow-up was 2 years (± 1.4). The mean preoperative ADL and IADL scores were correlated with a positive independence of the patient, while the mean postoperative scores corresponded to a moderate-low independence. Also the mean Mental and Physical SF12 scores saw a decrease in values. NLR values were higher in the first group of patients with complications. CONCLUSIONS: A careful multiparametric and multidisciplinary patient selection is required to identify the suitable patient to this treatment.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Distinct Patterns of Stromal and Tumor Expression of ROR1 and ROR2 in Histological Subtypes of Epithelial Ovarian Cancer.

OBJECTIVE: The ROR1 and ROR2 receptor tyrosine kinases have both been implicated in ovarian cancer progression and have been shown to drive migration and invasion. There is an increasing importance of the role of stroma in ovarian cancer metastasis; however, neither ROR1 nor ROR2 expression in tumor or stromal cells has been analyzed in the same clinical cohort. AIM: To determine ROR1 and ROR2 expression in ovarian cancer and surrounding microenvironment and examine associations with clinicopathological characteristics. METHODS: Immunohistochemistry for ROR1 and ROR2 was used to assess receptor expression in a cohort of epithelial ovarian cancer patients (n=178). Results were analyzed in relation to clinical and histopathological characteristics and survival. Matched patient sample case studies of normal, primary, and metastatic lesions were used to examine ROR expression in relation to ovarian cancer progression. RESULTS: ROR1 and ROR2 are abnormally expressed in malignant ovarian epithelium and stroma. Higher ROR2 tumor expression was found in early-stage, low-grade endometrioid carcinomas. ROR2 stromal expression was highest in the serous subtype. In matched patient case studies, metastatic samples had higher expression of ROR2 in the stroma, and a recurrent sample had the highest expression of ROR2 in both tumor and stroma. CONCLUSION: ROR1 and ROR2 are expressed in tumor-associated stroma in all histological subtypes of ovarian cancer and hold potential as therapeutic targets which may disrupt tumor and stroma interactions.

Quantitative 177Lu SPECT imaging using advanced correction algorithms in non-reference geometry.

Peptide receptor therapy with 177Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of 177Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher 177Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using µ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of 177Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators.

Gamma camera calibration and validation for quantitative SPECT imaging with (177)Lu.

Over the last years (177)Lu has received considerable attention from the clinical nuclear medicine community thanks to its wide range of applications in molecular radiotherapy, especially in peptide-receptor radionuclide therapy (PRRT). In addition to short-range beta particles, (177)Lu emits low energy gamma radiation of 113keV and 208keV that allows gamma camera quantitative imaging. Despite quantitative cancer imaging in molecular radiotherapy having been proven to be a key instrument for the assessment of therapeutic response, at present no general clinically accepted quantitative imaging protocol exists and absolute quantification studies are usually based on individual initiatives. The aim of this work was to develop and evaluate an approach to gamma camera calibration for absolute quantification in tomographic imaging with (177)Lu. We assessed the gamma camera calibration factors for a Philips IRIX and Philips AXIS gamma camera system using various reference geometries, both in air and in water. Images were corrected for the major effects that contribute to image degradation, i.e. attenuation, scatter and dead- time. We validated our method in non-reference geometry using an anthropomorphic torso phantom provided with the liver cavity uniformly filled with (177)LuCl3. Our results showed that calibration factors depend on the particular reference condition. In general, acquisitions performed with the IRIX gamma camera provided good results at 208keV, with agreement within 5% for all geometries. The use of a Jaszczak 16mL hollow sphere in water provided calibration factors capable of recovering the activity in anthropomorphic geometry within 1% for the 208keV peak, for both gamma cameras. The point source provided the poorest results, most likely because scatter and attenuation correction are not incorporated in the calibration factor. However, for both gamma cameras all geometries provided calibration factors capable of recovering the activity in anthropomorphic geometry within about 10% (range -11.6% to +7.3%) for acquisitions at the 208keV photopeak. As a general rule, scatter and attenuation play a much larger role at 113keV compared to 208keV and are likely to hinder an accurate absolute quantification. Acquisitions of only the (177)Lu main photopeak (208keV) are therefore recommended in clinical practice. Preliminary results suggest that the gamma camera calibration factor can be assessed with a standard uncertainty below (or of the order of) 3% if activity is determined with equipment traceable to primary standards, accurate volume measurements are made, and an appropriate chemical carrier is used to allow a homogeneous and stable solution to be used during the measurements.

Experimental determination of calibration settings of a commercially available radionuclide calibrator for various clinical measurement geometries and radionuclides.

Following the approach of the National Primary Laboratory of the UK (NPL) for the calibration of radionuclide calibrators, but using a commercially available instrument with no data available in the literature, the radionuclide calibrator response was investigated as a function of different measurement geometries at the "Regina Elena" National Cancer Institute (IRE) in Rome. Working with Italian National Metrology Institute for ionising radiation quantities (ENEA-INMRI), specific calibration factors with traceability to national primary standards were determined for different types of glass vials, solid capsules and plastic syringes, investigating three radionuclides with different energy spectra (Tc-99m, In-111, I-131). For each kind of syringe, calibration correction factors for different filling volumes were calculated. For Tc-99m and I-131 the difference between measured and true activity was in the range 2-7%, depending on measurement geometry. For In-111 a large percentage deviation from the true activity value was found in each geometry considered, reaching 35%. The magnitude of this difference is particularly dependent on the energies of the emitted photons.

Differences of regional coronary flow reserve assessed by adenosine thallium-201 scintigraphy early and six months after successful percutaneous transluminal coronary angioplasty or stent implantation.

This study assesses regional coronary flow reserve using adenosine thallium-201 scintigraphy early and 6 months after angiographically successful percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Seventeen consecutive men with a significant isolated left anterior descending coronary artery stenosis were scheduled for repeat coronary angiography and adenosine-planar thallium-201 scintigraphy within 24 hours and 6 months after successful PTCA (n = 8) or stent implantation (n = 9). After background subtraction, left ventricular segmental uptake was semiquantitatively assessed on thallium images. The perfusion defect severity was scored from 0 (normal) to 3. Coronary angiograms were analyzed using an automated edge contour detection computer analysis system. Data are expressed as mean value +/- 1 SD, and proportions as percentage. The residual narrowing was 17 +/- 8% after PTCA and 9 +/- 2% after stent implantation (p = 0.02). Twenty-four hours after the procedure, hypoperfused segments were detected in all patients (100%) and in 4 patients (44%) (p = 0.05), respectively. The total number of hypoperfused segments was greater after PTCA than after stent implantation (16 [40%] vs 7 [16%], p = 0.001, respectively) as was the perfusion defect severity (4.4 +/- 3.1 vs 1 +/- 1.2, p = 0.006). Six months after the procedure, 3 of the 5 patients who had undergone PTCA without restenosis still had reversible perfusion defects. None of the stent-treated patients had restenosis or reversible perfusion defects (p = 0.05). Among PTCA-treated patients without restenosis, the total number of hypoperfused segments and the perfusion defect severity were 9 of 25 (36%) and 0.8 +/- 0.8, respectively. Thus, a regional reduction in coronary flow reserve, occasionally observed early after successful stent implantation, is probably due to a transient alteration of small coronary vessels, as was also supported by the absence of perfusion defects 6 months after the procedure. The more severe impairment of regional coronary flow reserve observed early after successful PTCA is probably also due to angiographic underestimation of the residual stenosis, as suggested also by the persistence of reversible perfusion defects 6 months after the procedure in a few patients.

Drug-food interactions in clinical practice.

Drug-food interactions are a significant problem in clinical practice. Foods may alter the effects of drugs by interfering with pharmacokinetic processes, such as absorption and elimination. For example, absorption of tetracyclines is decreased when taken with milk or other dairy products. Pharmacologic and pharmacodynamic mechanisms also play an important role in drug-food interactions by altering drug effects. An example is the interaction of warfarin sodium with leafy green vegetables, whereby the hypoprothrombinemic effect of warfarin may be decreased and thromboembolic complications may develop. Similarly, certain drugs may have an effect on food intake, absorption, metabolism, and utilization. Numerous drugs, such as antineoplastic agents, have been shown to suppress appetite, resulting in decreased food intake and nutritional deficiency. It is important that health care providers, such as physicians, pharmacists, and dietitians, recognize and work as a team to prevent significant drug-food interactions. Minimizing adverse drug-food interactions would improve patient care by optimizing therapeutic effects and maintaining proper nutritional status.

Possible severe thrombocytopenia associated with a single dose of plicamycin.

OBJECTIVE: To report a case of possible severe thrombocytopenia associated with administration of a single dose of plicamycin. CASE SUMMARY: A 73-year-old man with prostate cancer was admitted to the hospital with hypercalcemia (total serum calcium concentration 4.02 mmol/L) and a low baseline platelet count (152 x 10(9)/L). Because of his symptomatic hypercalcemia, he was treated with NaCl 0.9%, furosemide, oral inorganic phosphate, and a single dose of plicamycin (15 micrograms/kg). Five days after plicamycin administration his platelet count decreased to 52 x 10(9)/L, and continued to decrease further even after the transfusion of four units of platelets to a nadir of 7 x 10(9)/L (hospital day 20). A second transfusion produced a small increase in his platelet count. The patient's clinical status continued to deteriorate, however, and he subsequently died. DISCUSSION: Plicamycin and other drugs that may induce thrombocytopenia are reviewed. The time course between plicamycin administration and the development of thrombocytopenia in our patient is assessed. Other contributing factors such as a low baseline platelet count and advanced age are also addressed. CONCLUSIONS: It is likely that the severe thrombocytopenia experienced by our patient was caused by a single dose of plicamycin. Adjusting the dosage for a patient's renal function as well as close monitoring of the platelet count are necessary when administering this drug. We report this case to remind clinicians of the potential for the development of severe thrombocytopenia following administration of a single dose of plicamycin.

Transcriptional regulation of prolactin receptor gene expression by sodium butyrate in MCF-7 human breast cancer cells.

The prolactin receptor (PRLR) mediates the diverse effects of prolactin, which in the mammary gland include the development of lobuloalveolar structures and increased tumor cell proliferation. Treatment of mammary carcinoma cells with the differentiating agent sodium butyrate (NaB) is known to reduce PRLR binding activity and PRLR gene expression, however the mechanism which mediates these changes is unknown, prompting this investigation. Using MCF-7 human breast cancer cells, assay of the rate of PRLR gene transcription by the nuclear run-on technique indicated that 3 mM NaB reduced PRLR gene transcription by 50% after 3 h of treatment and that this effect was maintained for at least 24 h. The protein synthesis inhibitor cycloheximide failed to abrogate this effect, which indicated that NaB did not require continuing protein synthesis to reduce the rate of PRLR transcription. Measurement of PRLR mRNA stability, using Northern blot analysis at various times after the inhibition of transcription with actinomycin D, showed that NaB treatment did not alter PRLR mRNA half-life. These results indicate that NaB inhibits PRLR gene expression by a transcriptional mechanism that does not require continuing protein synthesis.

Coordinate regulation of oestrogen and prolactin receptor expression by sodium butyrate in human breast cancer cells.

Prolactin receptor and oestrogen receptor are co-ordinately expressed in human breast cancer cell lines and in human breast tumour biopsies, leading to the suggestion that the expression of these receptors may be coupled. To examine this hypothesis, T-47D and MCF-7 human breast cancer cells were treated with sodium butyrate, a known modulator of oestrogen receptor levels, and the changes in oestrogen and prolactin receptor mRNA and binding activity were measured. In both cell lines treatment with 0.3-10 mM sodium butyrate resulted in a parallel decrease in prolactin and oestrogen receptor mRNA levels and binding activity. In T-47D cells, where the effect was transient, mRNA levels of both receptors recovered in parallel. These data indicated that oestrogen receptor and prolactin receptor gene expression is modulated in parallel by sodium butyrate and supported the hypothesis that the expression of these two receptors is coupled.

[The role of endorectal echography for determining the extent of an operation]. / Rol' éndorektal'noi ékhografii dlia opredeleniia ob''ema operatsii.

The paper discusses the usefulness of endorectal echotomography and adenolymphoscintigraphy--two new diagnostic methods which allow surgeons to know preoperatively tumor extension beyond the rectal wall and lymph nodes involvement. Though the statistical data presented are not numerous, it is hoped that, using these two diagnostic methods in cases of rectal tumors, surgeons will be able to choose better between local excision and abdominoperineal resection thus avoiding unnecessary and mutilating operations.

Pilonidal sinus with an anal canal fistula. Report of a case.

A rare case of a pilonidal cyst with the fistulous tract situated inside the anal canal is described. This is the sixth such case in the medical literature.

Evaluation of tricyclic antidepressant plasma levels by an automated enzyme immunoassay (EMIT) in comparison to a high-performance liquid chromatographic method.

A new homogeneous enzyme immunoassay technique (EMIT) for the measurement of plasma levels of amitriptyline, nortriptyline, imipramine, and desipramine was used with an automated procedure and the results were compared to those of a high-performance liquid chromatographic (HPLC) method. Precision of the EMIT test was similar to that of the HPLC method with within-day coefficients of variation in the range of 3.9-10.9% (EMIT) and 3.9-9.6% (HPLC). The day-to-day coefficients of variation ranged from 4.4 to 11.7% for EMIT and from 6.1 to 8.4% for HPLC. Samples from 124 patients were analyzed by both methods and a good correlation was observed for all the four drugs. A paired t test indicated no significant difference for the EMIT and HPLC values. No significant interferences were observed between the tricyclics tested and other commonly associated drugs, such as benzodiazepines and neuroleptics. The new EMIT assay proved to be rapid and easy to perform and showed sufficient reliability and reproducibility to be used for either emergency or routine analysis.

Immunohistochemical identification of proliferating cells in organ culture using bromodeoxyuridine and a monoclonal antibody.

The ability to measure cell proliferation is important in the study of cancer biology. The usual technique for quantitating proliferating cells in tissue explant and organ culture by detection of [3H]-thymidine incorporation into DNA by autoradiography is tedious and time-consuming. We have developed a technique for identification and quantitation of bromodeoxyuridine (an analogue of thymidine) in cultured tissue explants. Fetal mouse colon explants were exposed in vitro to bromodeoxyuridine (BUdR) or [3H]-thymidine for 3 to 72 hr and then for various periods to unlabeled thymidine. The tissues were stained with a monoclonal anti-bromodeoxyuridine antibody and in parallel [3H]-thymidine incorporation was detected by autoradiography. Incorporation of BUdR was measured by quantitating the amount of pigment deposited over nuclei after immunohistochemical staining, using an optical data digitizer. It was found that both techniques identified proliferating cells. Dividing cells were present both in crypts and in the surrounding stroma in Day 14 fetal mouse colon cultures. The immunohistochemical technique was more rapid and less cumbersome than autoradiography.

The Omenn's syndrome: histological, immunohistochemical and ultrastructural evidence for a partial T cell deficiency evolving in an abnormal proliferation of T lymphocytes and S-100 +/T-6 + Langerhans-like cells.

A 7 month old female infant was affected by a rapidly fatal familial disease highly reminiscent of Omenn's syndrome. She presented with widespread eczematous lesions, hepatosplenomegaly, superficial lymphadenopathy, peripheral blood lymphocytosis, eosinophilia and hyper-IgE. An axillary lymph node was involved by a marked proliferation of T-3 +/T-10-- lymphocytes admixed with S-100+/T-6+/Leu-3a+/Ia + reticular cells which lacked typical LC granules; cell suspension study revealed that 90%-96% of the lymph node cells were T-11+/T-3+ lymphocytes characterized by low expression of Leu-3a and T-8 antigens and by high expression of Ia antigens (52%). Peripheral blood T lymphocytes exhibited a similar distribution of surface phenotypes. The patient died of interstitial pneumonia and an autopsy was performed. The thymus was markedly atrophic and completely devoid of lymphocytes. The peri-arteriolar lymphoid sheets of the spleen were poorly developed and were mainly composed of T-8+ lymphocytes. The mediastinal nodes were rudimentary and were populated by T-3+/T-10+ lymphocytes with low expression of Leu-3a and T-8 antigens. Our results raise the possibility that Omenn's syndrome is a peculiar primary immunodeficiency in which, despite early thymic involution, some abnormal T lymphocytes still develop in the peripheral lymphoid organs. Antigenic triggering of these cells might result in prominent proliferations of T lymphocytes and Langerhans-like cells which lead to the clinical manifestation of the disease.