To protect or not to protect: examining reasons for sun protection among young women at risk for skin cancer.

We aimed to further the understanding of the low rates of sun protection in young women at risk for skin cancer. Six-hundred-sixty-one daily diary entries were received via text message over 14 days from 56 young women at moderate to high risk of developing skin cancer. Women reported whether or not they used sun protection and also listed what their reasons were for using protection or not using sun protection each day. Multi-level modeling was used to examine the influence of study variables when predicting daily sun protection or lack of protection. The number of days in which sun protection was reported was positively associated with "habit" and "prevention" as reasons for protection and negatively associated with "not-needed" and "unprepared" as reasons for non-protection. Self-reported sun protection increased over the 14-day study period. Results of this study suggest the potential value of interventions aimed at motives for sun-protection behaviors.

International consensus statement on the peri-operative management of anaemia and iron deficiency.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.

In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources.

Retrospective Investigations of Recurring Histomonosis on a Turkey Farm.

The ban of effective feed additives and therapeutics in the European Union and in other parts of the world led to a dramatic increase of histomonosis in turkeys. Despite the impact of the disease on the health and welfare of poultry, many questions remain open regarding the epidemiology of the pathogen. In this study, we retrospectively monitored a farm with recurring cases of histomonosis to identify possible routes of pathogen introduction and predisposing factors that may influence the disease development. We included 32 consecutive turkey flocks, which were fattened between 2007 and 2021 on the same farm under the same management and housing conditions. During this period, Histomonas meleagridis was detected in eight flocks of toms and four flocks of hens with a high variability in disease development. Outbreaks in toms led to significantly (P ≤ 0.05) higher mortality rates (5.3%-98.3%) than in hens (2.6%-6.1%). Most of the outbreaks (9/12) were diagnosed between June and September with a peak in August, suggesting a possible impact of higher temperatures either on the host or on the pathogen and pathogen-transmitting vectors. Further investigation is necessary to determine why hens might cope better with histomonosis than toms. Continuous flock and hygiene management is important to prevent an introduction of the causative pathogen and to control potential vectors.

Investigaciones retrospectivas de histomoniasis recurrente en una granja de pavos. La prohibición de aditivos alimentarios y productos terapéuticos efectivos en la Unión Europea y en otras partes del mundo condujo a un aumento dramático de histomoniasis en pavos. A pesar del impacto de la enfermedad en la salud y el bienestar de las aves, quedan muchas interrogantes abiertas con respecto a la epidemiología del patógeno. En este estudio, se monitoreó retrospectivamente una granja con casos recurrentes de histomoniasis para identificar posibles rutas de introducción de patógenos y factores predisponentes que puedan influir en el desarrollo de la enfermedad. Se incluyeron 32 lotes de pavos consecutivos, que fueron engordados entre 2007 y 2021 en la misma granja bajo las mismas condiciones de manejo y alojamiento. Durante este período, se detectó Histomonas meleagridis en ocho parvadas de machos y cuatro parvadas de gallinas con una alta variabilidad en el desarrollo de la enfermedad. Los brotes en machos llevaron a tasas de mortalidad significativamente más altas (P ≤ 0.05) (5.3 %­ - 98.3 %) que en gallinas (2.6 %­ - 6.1 %). La mayoría de los brotes (9/12) se diagnosticaron entre junio y septiembre con un pico en agosto, lo que sugiere un posible impacto de las temperaturas más altas sobre el huésped o en el patógeno y los vectores transmisores del patógeno. Se necesita más investigación para determinar por qué las gallinas pueden sobrellevar mejor la histomoniasis que los machos. El manejo continuo de la parvada y la higiene es importante para prevenir la introducción del patógeno causante y controlar a los vectores potenciales.

Death from metastatic donor-derived ovarian cancer in a male kidney transplant recipient.

Posttransplant malignancy developing in an allograft is an uncommon complication of organ transplantation. The tumor may represent malignant transformation of donor or recipient cells that were previously normal, metastatic malignancy of recipient origin or malignancy transmitted from organ donor to recipient. Establishing the origin of the malignancy is critical to treatment algorithms. It is generally believed allograft removal and immunosuppression withdrawal will lead to resolution of transmitted malignancies in cases where the renal allograft is the origin. We report a male patient who developed metastatic ovarian malignancy secondary to donor transmission.

Low-molecular weight iron dextran and iron sucrose have similar comparative safety profiles in chronic kidney disease.

Serious adverse events that occur with the administration of iron dextran are due to the high molecular weight preparations. Conclusions that iron sucrose and ferric gluconate are safer than iron dextran may be premature. Published literature comparing safety profiles of available parenteral iron products is reviewed. Administration of iron salts to pre-dialysis patients with chronic kidney disease may not be optimal. We recommend the total dose infusion of low molecular weight iron dextran as an option for iron replacement.

A quick, direct method that can differentiate expressed mitochondrial genes from their nuclear pseudogenes.

Direct sequencing of mitochondrial DNA (mtDNA) following amplification using the polymerase chain reaction (PCR) has found widespread use in population genetic and phylogenetic research over the past few years. Recently, nuclear copies of mitochondrial genes have been reported in diverse eukaryotic species, often confounding such research (reviewed in [2,3]). Under certain circumstances, nuclear pseudogenes can be amplified more efficiently than the intended mtDNA target, even when using as template mtDNA that has been purified by gradient centrifugation. If the transfer of the gene copy to the nucleus happened recently, it can be difficult-if not impossible-to identify the legitimate mitochondrial sequence. Here, we present a simple method that can identify expressed mitochondrial genes, using the cytochrome b gene of the particularly problematical proboscis monkey as an example. Because mtDNA is transcribed and processed into polyadenylated mRNAs reverse transcription coupled to PCR can be used to amplify the expressed mitochondrial version. This method produced an unambiguous sequence for the proboscis monkey mitochondrial cytochrome b gene; in contrast, traditional DNA-based PCR methods produced ambiguous sequence, because many nuclear pseudogenes were present. Phylogenetic analysis of the cytochrome b gene suggests that the proboscis monkey groups with the Asian langurs, rather than forming a sister taxon to all Asian and African colobines as was previously suggested. Reverse transcriptase-coupled PCR should be applicable to many other cases of nuclear transfer of mtDNA, including those involving ribosomal genes.

Measurement of desarginine fibrinopeptide B in human blood.

Thrombin converts fibrinogen to fibrin in two steps. First fibrinopeptide A and fibrin I are formed and then fibrinopeptide B (B beta 1-14) and fibrin II. Since it is postulated that fibrin II is important in the genesis of thrombosis, it is of interest to measure fibrinopeptide B in peripheral blood samples. Previous difficulties in interpreting fibrinopeptide B immunoreactivity in plasma resulted from crossreaction of fibrinogen and of plasmin digest peptides B beta 1-42 and B beta 1-21 and from rapid loss of fibrinopeptide B immunoreactivity resulting from cleavage of arginine 14 by blood carboxypeptidase B. We have obviated these difficulties by removing fibrinogen from plasma by precipitation with ethanol and peptides B beta 1-21 and B beta 1-42 by adsorption on bentonite. Fibrinopeptide B is then converted to a desarginine fibrinopeptide B, which is measured in a new specific assay. Studies of the kinetics of fibrinopeptide cleavage showed that when whole blood was allowed to clot in vitro, fibrinopeptide A was cleaved more rapidly than fibrinopeptide B. In 18 patients on an acute care medical ward, desarginine fibrinopeptide B levels were lower than fibrinopeptide A levels and did not correlate with the levels of fibrinopeptide A or B beta 1-42. Desarginine fibrinopeptide B levels were less than 1 pmol/ml in all but two patients. In six patients receiving intraamniotic infusions of hypertonic saline to induce abortion, desarginine fibrinopeptide B levels increased 10-fold from the preinfusion mean level of 0.4 pmol/ml and then decreased. The pattern of changes resembled that of the fibrinopeptide A levels rather than of the B beta 1-42 levels. On the basis of these data it is suggested that plasma desarginine fibrinopeptide B levels reflect fibrin II formation in vivo.

Novel features in a patient homozygous for the L347P mutation in the PINK1 gene.

The purpose of this study was to assess the genotype-phenotype of PINK1 mutations. We genotyped eight known mutations in three clinic-based cohorts with Parkinsonism and found one homozygous p.L347P mutation in PINK1. Clinically, hypo-osmia and profound diurnal variation of symptoms were identified as novel features; fluorodopa positron emission tomography revealed striking decline in striatal fluorodopa uptake. We suggest that it may be possible to clinically separate this form of Parkinsonism from dopa-responsive dystonia and Parkin-related Parkinsonism. Furthermore, as this mutation has only been reported in Filipinos (two originated from Luzon island), our results support the hypothesis of a common founder.

Prevalence of myocardial viability as detected by positron emission tomography in patients with ischemic cardiomyopathy.

BACKGROUND: Detection of myocardial viability is important in patients with ischemic cardiomyopathy. Restoration of blood flow to viable myocardium is associated with improved left ventricular function and improved patient prognosis. However, the prevalence of viable myocardium in patients with ischemic cardiomyopathy is unknown. METHODS AND RESULTS: To determine the prevalence of myocardial viability, clinical [13N]ammonia/18F-deoxyglucose PET studies performed in 283 patients (age, 63+/-10 years) with ischemic heart disease (mean ejection fraction, 26+/-8%) were visually analyzed for the presence and extent of viable and nonviable myocardium. The myocardium was divided into 19 segments. The extent of viable myocardium was considered "functionally" significant if >/=5 segments ( approximately 25% of the left ventricular myocardium) exhibited a blood flow/metabolism mismatch and "prognostically" significant if 1 to 4 left ventricular segments did so. Of all patients, 41% had no evidence of viable myocardium, 55% had viable myocardium, and 4% had normal blood flow and metabolism within an enlarged left ventricle. Functionally significant viability was found in 27% and prognostically significant viability in 28% of the patients. Multivariate analysis revealed the presence of angina to be the only clinical parameter associated with the presence of functionally significant viability. CONCLUSIONS: Revascularization might improve patient prognosis in 55% and result in improved left ventricular function in 27% of all patients with ischemic cardiomyopathy.

Performance of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography and integrated PET/CT in restaged breast cancer patients.

PURPOSE: This study was conducted to compare the clinical stage derived from 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) positron emission tomography (PET) to that of integrated PET/computed tomography (CT) in restaged breast cancer patients. PROCEDURES: Fifty-eight female patients (age range 29-80 years, mean age +/-SD, 53.3 +/- 11.7 years) underwent PET/CT restaging for breast cancer. Two experienced nuclear medicine physicians interpreted PET images. A radiologist was added for reading PET/CT studies. A patient-based analysis was performed. Histopathological findings, correlative imaging studies, changes in number, size, and hypermetabolic activity of suspicious lesions and/or patient outcome served as standard of reference for determining the diagnostic accuracy of both modalities. RESULTS: PET staged 79.3% (46/58) of the patients correctly, overstaged seven (12.1%), and understaged five patients (8.6%). Integrated PET/CT staged 89.7% (52/58) of the patients correctly, overstaged four (6.9%), and understaged two patients (3.4%). The staging accuracy of PET/CT was not significantly better than that of PET alone (p = 0.059). Lesions exhibiting mild hypermetabolic activity, benign inflammatory lesions, and physiological variants largely explained incorrect PET findings. CONCLUSION: Integrated PET/CT only marginally improves the restaging accuracy over PET alone (p = 0.059) in breast cancer patients.

Hexamethylene bisacetamide in myelodysplastic syndrome: effect of five-day exposure to maximal therapeutic concentrations.

The efficacy of hexamethylene bisacetamide (HMBA), a potent polar-planar solvent which is capable of differentiating leukemias and solid tumors in vitro at clinically achievable concentrations, was studied in 16 patients with severe myelodysplastic syndromes (MDS). An adaptive control dosing algorithm was used to maintain HMBA steady-state concentrations (Css) within a narrow therapeutic window (1-2 mM) for five days every four weeks. Despite achieving the target HMBA Css during at least two courses in each of 15 patients, HMBA did not produce clinically relevant improvements in blood cell counts nor in other functional indices. Instead, HMBA induced cytopenias in the majority of these patients, most of whom had preexisting cytopenias and limited hematopoietic reserves. These disappointing results correlated with concurrent in vitro bone marrow studies from these patients in which both the HMBA concentrations that were optimal for differentiation in vitro (2-5 mM) and the HMBA Css that were achieved in this study (1-2 mM) substantially inhibited the growth of granulocyte-macrophage colony-forming units and erythroid burst-forming units. Although the mechanism responsible for the anti-proliferative effects of HMBA on hematopoietic progenitors (cytotoxicity versus terminal differentiation) could not be determined, the induction of cytopenias and lack of significant clinical improvements suggest that HMBA is cytotoxic and will not be useful alone as a differentiating agent on this schedule of administration in the treatment of MDS.

Clinical PET/CT imaging: promises and misconceptions.

PET/CT is now established as the most important imaging tool in oncology. PET/CT stages and restages cancer with a higher accuracy than PET or CT alone. The sometimes irrational approach to combine state of the art PET with the highest end CT devices should give way to a more reasonable equipment design tailored towards the specific clinical indications in well-defined patient populations. The continuing success of molecular PET/CT now depends more upon advances in molecular imaging with the introduction of targeted imaging probes for individualized therapy approaches in cancer patients and less upon technological advances of imaging equipment.

SPECT- and PET-based patient-tailored treatment in neuroendocrine tumors: a comprehensive multidisciplinary team approach.

The overexpression of somatostatin receptors on the tumor cell surface of neuroendocrine tumors (NETs) detected by multimodal functional imaging modalities such as SPECT and PET tracers constitutes a therapeutic option using targeting radiolabeled compounds. We will introduce the theranostic concept in general, explain in more detail its development in NETs, and discuss available SPECT and PET tracers regarding their potential for diagnostic imaging, visualization of target expression, and treatment tailoring. Moreover, we will discuss the currently available peptide receptor radionuclide therapy principles and compare them to previously published studies. Finally, we will discuss which new concepts will most likely influence the theranostic treatment approach in NETs in the future.

Acute myeloid leukemia in patients more than 50 years of age: special considerations in diagnosis, treatment, and prognosis.

Although most patients with acute myeloid leukemia are more than 50 years of age and age is known to be an adverse prognostic factor, relatively few studies have been conducted to determine the optimum treatment strategy for the older patient. This report suggests that, until definitive studies are conducted in this age group, intensive chemotherapy should always be considered if the older patient's overall status and desires are consistent with this approach. Other factors, specifically cytogenetic and cell-surface marker findings, provide prognostic information, independent of age, and should also be considered during patient management.

Systemic babesiosis. Another cause of the hemophagocytic syndrome.

Hemophagocytosis is a pathologic finding in a variety of infectious diseases associated with peripheral pancytopenia. In addition, hemophagocytosis is a prominent finding in malignant histiocytosis, a primary disorder of the monocyte-macrophage system. Systemic babesiosis is a rare parasitic disorder associated with intraerythrocytic parasites in the peripheral blood. There has been no description of the marrow findings in this disorder. A patient is described who had systemic babesiosis and prominent hemophagocytosis that disappeared after appropriate antiparasitic therapy. Systemic babesiosis should be considered in the differential diagnosis of hemophagocytosis.

Early increased chemokine expression and production in murine allogeneic skin grafts is mediated by natural killer cells.

BACKGROUND: Increased expression of chemokine mRNA is observed in allogeneic but not syngeneic skin grafts 3-4 days after transplantation. The recipient cells mediating this early inflammatory response in allografts remain unidentified. METHODS: Isogeneic and allogeneic skin grafts were transplanted to euthymic and athymic nude mice. mRNA expression and protein production of macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and the murine homolog of Gro(alpha), i.e. KC, from graft homogenates retrieved 3-4 days posttransplantation was tested by Northern blot hybridization and ELISA. To deplete NK cells, recipients were treated with antiasialo GM1 (ASGM1) antisera or with anti-NK1.1 mAb before transplantation. RESULTS: Expression of KC, MIP-1alpha, and MIP-1beta mRNA was equivalent in C57BL/6 allogeneic skin grafts and BALB/c isografts at day 2 posttransplant. At day 3 posttransplant, chemokine mRNA levels decreased in isografts but were maintained at high levels in the allografts. Increased early chemokine mRNA was also observed in C57BL/6, but not BALB/c++ grafts on BALB/c athymi(nu/nu) recipients. Treatment of allograft recipients with ASGM1 or with anti-NK1.1 antibody eliminated NK cells from the spleen and allograft infiltrating cell populations and decreased early chemokine mRNA levels in allografts 60-70%. Analyses of allograft homogenates indicated increased levels of KC, MIP-1alpha, and MIP-1beta protein at day 4 posttransplant that were decreased in recipients depleted of NK cells. Early chemokine mRNA levels were equivalent in isogeneic and semiallogeneic F1 grafts. CONCLUSIONS: Early chemokine mRNA expression and protein production in allogeneic skin grafts is amplified by recipient natural killer (NK) cells. These results indicate a novel function for infiltrating NK cells in mediating early increased intra-allograft chemokine production and inflammation during the initiation of acute rejection.

Effects of modified pharmacologic stress approaches on hyperemic myocardial blood flow.

UNLABELLED: Pharmacologic stress testing with 0.56 mg/kg of intravenous dipyridamole is frequently used to noninvasively detect coronary artery disease (CAD). However, high-dose dipyridamole (0.80 mg/kg) or the combination of standard-dose dipyridamole (0.56 mg/kg) with the isometric handgrip maneuver might evoke a greater coronary hyperemic response. METHODS: To evaluate the effect of modified pharmacologic stress tests, myocardial blood flow as quantified in 11 male subjects (mean age: 27 +/- 7 yr) during standard-dose dipyridamole (0.56 mg/kg), high-dose dipyridamole (0.80 mg/kg) and standard-dose dipyridamole combined with the isometric handgrip exercise using dynamic PET and a two-compartment model for 13N-ammonia. RESULTS: Systolic blood pressure, heart rate and rate pressure product remained unchanged from standard to high-dose dipyridamole but increased with the addition of the isometric handgrip. Myocardial blood flow was unchanged from standard to high-dose dipyridamole but was lower with the addition of the isometric handgrip. CONCLUSION: The hyperemic response induced by standard-dose dipyridamole cannot be further enhanced by high-dose dipyridamole. The addition of the isometric handgrip exercise results in a modest, but significant decline in hyperemic blood flow possibly due to increased extravascular resistive forces or an increase in a mediated coronary vasoconstriction associated with exercise.

A randomized trial of three iron dextran infusion methods for anemia in EPO-treated dialysis patients.

Forty-three hemodialysis patients receiving recombinant erythropoietin (rHuEPO, epoietin alpha) were randomized to receive intravenous iron dextran as a total-dose infusion, 500-mg infusion to total dose, or 100-mg bolus to total dose, in each case during the dialysis procedure. The dose of iron dextran was calculated from the patient's existing hemoglobin to achieve a desired hemoglobin. Patients were eligible to receive intravenous iron dextran if they had a serum ferritin of < or = 100 ng/mL or a serum ferritin of 100 to 200 ng/mL, along with a transferrin saturation of < or = 19%. Patients were excluded if they had prior therapy with iron dextran, aluminum intoxication, or transfusion during the study. The time to the maximum hemoglobin, acute adverse reactions, and delayed adverse reactions were analyzed statistically, and no differences were seen in any of the three groups. Total-dose intravenous iron dextran infusion is safe, convenient, less expensive, and as efficacious as divided-dose infusions.