Neural Transformers for Intraductal Papillary Mucosal Neoplasms (IPMN) Classification in MRI images.

Early detection of precancerous cysts or neoplasms, i.e., Intraductal Papillary Mucosal Neoplasms (IPMN), in pancreas is a challenging and complex task, and it may lead to a more favourable outcome. Once detected, grading IPMNs accurately is also necessary, since low-risk IPMNs can be under surveillance program, while high-risk IPMNs have to be surgically resected before they turn into cancer. Current standards (Fukuoka and others) for IPMN classification show significant intra- and inter-operator variability, beside being error-prone, making a proper diagnosis unreliable. The established progress in artificial intelligence, through the deep learning paradigm, may provide a key tool for an effective support to medical decision for pancreatic cancer. In this work, we follow this trend, by proposing a novel AI-based IPMN classifier that leverages the recent success of transformer networks in generalizing across a wide variety of tasks, including vision ones. We specifically show that our transformer-based model exploits pre-training better than standard convolutional neural networks, thus supporting the sought architectural universalism of transformers in vision, including the medical image domain and it allows for a better interpretation of the obtained results.

Genitourinary manifestations of endometriosis with emphasis on the urinary tract.

Endometriosis is a common benign condition affecting women. The disease has a broad spectrum of presentations from incidental lesions in asymptomatic women to causing significant and debilitating morbidity in others. Ectopic endometrial glands are located in predictable locations throughout the pelvis, including implantation on the ovaries and in the rectouterine cul-de-sac. Less commonly, the urinary tract may be involved. As genitourinary manifestations may remain symptomatically occult or masquerade as other diagnoses, it is essential for the radiologist to be aware of the imaging features, consider this diagnosis, and potentially save the patient from delayed treatment.

Detection of metabolites of trapped humans using ion mobility spectrometry coupled with gas chromatography.

For the first time, ion mobility spectrometry coupled with rapid gas chromatography, using multicapillary columns, was applied for the development of a pattern of signs of life for the localization of entrapped victims after disaster events (e.g., earthquake, terroristic attack). During a simulation experiment with entrapped volunteers, 12 human metabolites could be detected in the air of the void with sufficient sensitivity to enable a valid decision on the presence of a living person. Using a basic normalized summation of the measured concentrations, all volunteers involved in the particular experiments could be recognized only few minutes after they entered the simulation void and after less than 3 min of analysis time. An additional independent validation experiment enabled the recognition of a person in a room of ∼25 m(3) after ∼30 min with sufficiently high sensitivity to detect even a person briefly leaving the room. Undoubtedly, additional work must be done on analysis time and weight of the equipment, as well as on validation during real disaster events. However, the enormous potential of the method as a significantly helpful tool for search-and-rescue operations, in addition to trained canines, could be demonstrated.

Persistence of recipient plasma cells and anti-donor isohaemagglutinins in patients with delayed donor erythropoiesis after major ABO incompatible non-myeloablative haematopoietic cell transplantation.

Delayed donor erythropoiesis and pure red-cell aplasia (PRCA) complicate major-ABO mismatched non-myeloablative allogeneic stem-cell transplantation. To characterize these events, we analysed red-cell serology and chimaerism in lymphohaematopoietic lineages, including plasma cells and B cells, in 12 consecutive major-ABO incompatible transplants following cyclophosphamide/fludarabine-based conditioning. Donor erythropoiesis was delayed to more than 100 days in nine (75%) patients including six (50%) who developed PRCA. During PRCA, all patients had persistent anti-donor isohaemagglutinins and recipient plasma cells (5-42%), while myeloid and T cells were completely donor in origin. In contrast, B-cell chimaerism was frequently full-donor when significant anti-donor isohaemagglutinins persisted. Four patients with early mixed haematopoietic chimaerism and the prolonged presence of anti-donor isohaemagglutinins and recipient plasma cells developed delayed-onset (>100 days post-transplant) red cell transfusion dependence and PRCA after myeloid chimaerism converted from mixed to full donor. These findings confirm that donor-erythropoiesis is impacted by temporal disparities in donor immune-mediated eradication of recipient lymphohaematopoietic cells during major-ABO incompatibility and suggest that plasma cells are relatively resistant to graft-versus-host haematopoietic effects.

Transfusion medicine management for reconstructive spinal repair in a patient with von Willebrand's disease and a history of heavy surgical bleeding.

STUDY DESIGN: A case report of a multidisciplinary approach to a second reconstructive back surgery in a patient with von Willebrand's disease, flatback syndrome, and a history of heavy surgical bleeding is presented. OBJECTIVE: To review the perioperative planning and assessment of hemostasis and transfusion medicine management, including administration of Humate P, a Factor VIII preparation with high von Willebrand factor content. SUMMARY OF BACKGROUND DATA: Reconstructive spinal procedures may require significant transfusion support even in patients with normal preoperative hemostasis. In addition to the hemostatic problem caused by von Willebrand's disease, the reported patient requested minimal exposure to allogeneic blood products because of hepatitis C infection acquired from previous transfusions. METHODS: The multidisciplinary team included the patient, hematologist, blood bank medical director, anesthesiologist, and operating surgeon. Preoperative assessment showed a Type 2A von Willebrand's disease variant. A careful planning process included a test infusion of desmopressin and extensive autologous donations of red cells, plasma, and platelets, which were collected before the procedure. RESULTS: Anterior and posterior spine fusions were performed during a 14-hour procedure. Hemostasis and clinical response were excellent. Humate P was administered perioperatively as assessed by the baseline Factor VIII and von Willebrand's disease levels, the plasma volume, the half-life of infused Humate P, and the anticipated risk and tolerance for bleeding. The estimated blood loss was 5 L. Replacement included 9 units of autologous red cells, 6 units of autologous plasma, 2 autologous plateletpheresis collections, a single allogeneic plateletpheresis product, and 17,000 units of Humate P administered over the perioperative period. CONCLUSIONS: Using a careful multidisciplinary approach, excellent hemostasis can be achieved with minimal exposure to untreated allogeneic blood products during aggressive spinal surgery in a patient with a clinically significant congenital coagulopathy.

Comprehensive analysis of citrate effects during plateletpheresis in normal donors.

BACKGROUND: Although plateletpheresis procedures are generally well tolerated, the clinical and metabolic consequences associated with rapid infusion of up to 10 g of citrate are underappreciated, and a comprehensive description of these events is not available. STUDY DESIGN AND METHODS: Clinical and laboratory changes were studied in seven healthy donors undergoing three 90-minute plateletpheresis procedures each, at continuous, fixed citrate infusion rates of 1.1, 1.4, and 1.6 mg per kg per minute. RESULTS: Serum citrate levels increased markedly with increasing citrate infusion rates and did not achieve a stable plateau. As citrate infusion rates increased, the total volume processed and platelet yields also increased, but donor symptoms became more severe. Ionized calcium (iCa) and ionized magnesium (iMg) concentrations decreased markedly, by 33 and 39 percent below baseline, respectively, at a citrate rate of 1.6 mg per kg per minute. Intact parathyroid hormone levels were higher at 30 minutes than at later time points, despite progressive decreases in iCa and iMg. Urine citrate, calcium, magnesium, sodium, and potassium concentrations and urine pH values increased markedly during all procedures. CONCLUSION: Marked, progressive increases in serum citrate levels occur during plateletpheresis, accompanied by symptomatic decreases in iCa and iMg, with significantly increased renal excretion of calcium, magnesium, and citrate.

Delayed donor red cell chimerism and pure red cell aplasia following major ABO-incompatible nonmyeloablative hematopoietic stem cell transplantation.

Delayed donor red cell engraftment and pure red cell aplasia (PRCA) are well-recognized complications of major ABO-incompatible hematopoietic stem cell transplantation (SCT) performed by means of myeloablative conditioning. To evaluate these events following reduced-intensity nonmyeloablative SCT (NST), consecutive series of patients with major ABO incompatibility undergoing either NST (fludarabine/cyclophosphamide conditioning) or myeloablative SCT (cyclophosphamide/high-dose total body irradiation) were compared. Donor red blood cell (RBC) chimerism (initial detection of donor RBCs in peripheral blood) was markedly delayed following NST versus myeloablative SCT (median, 114 versus 40 days; P <.0001) and strongly correlated with decreasing host antidonor isohemagglutinin levels. Antidonor isohemagglutinins declined to clinically insignificant levels more slowly following NST than myeloablative SCT (median, 83 versus 44 days; P =.03). Donor RBC chimerism was delayed more than 100 days in 9 of 14 (64%) and PRCA occurred in 4 of 14 (29%) patients following NST, while neither event occurred in 12 patients following myeloablative SCT. Conversion to full donor myeloid chimerism following NST occurred significantly sooner in cases with, compared with cases without, PRCA (30 versus 98 days; P =.008). Cyclosporine withdrawal appeared to induce graft-mediated immune effects against recipient isohemagglutinin-producing cells, resulting in decreased antidonor isohemagglutinin levels and resolution of PRCA following NST. These data indicate that significantly delayed donor erythropoiesis is (1) common following major ABO-incompatible NST and (2) associated with prolonged persistence of host antidonor isohemagglutinins. The clinical manifestations of these events are affected by the degree and duration of residual host hematopoiesis.

MCV as a guide to phlebotomy therapy for hemochromatosis.

BACKGROUND: A multitude of recommendations exist for laboratory assays to monitor the pace and endpoints of phlebotomy therapy for hemochromatosis. All of these recommendations rely on an assessment of storage iron to guide treatment, and none have been prospectively evaluated. STUDY DESIGN AND METHODS: Nine consecutive patients underwent serial monitoring of Hb, MCV, transferrin saturation, and ferritin during weekly phlebotomy to deplete iron stores (induction therapy) and less frequent sessions to prevent iron reaccumulation (maintenance therapy). Changes in MCV and Hb were used to guide the pace of phlebotomy over a median of 7 years of follow-up. RESULTS: During induction therapy, the MCV increased transiently because of reticulocytosis and then stabilized for a prolonged period before decreasing more sharply, which reflected iron-limited erythropoiesis. Iron depletion was achieved after a median of 38 phlebotomies and removal of 9.0 g of iron. Maintenance phlebotomy was targeted to maintain the MCV at 5 to 10 percent below prephlebotomy values and the Hb at >13 g per dL. Transferrin saturation fluctuated considerably during treatment, but remained below 35 percent during MCV-guided maintenance therapy. Ferritin values were not useful guides to the pace of phlebotomy. The median maintenance therapy phlebotomy interval was 7.5 weeks (range, 6-16), which corresponded to an average daily iron removal of 35 to 67 microg per kg. Most patients showed evidence of iron reaccumulation at phlebotomy intervals of 8 weeks or more. CONCLUSION: The MCV is an inexpensive, precise, physiologic indicator of erythropoietic iron availability. When used in conjunction with the Hb, it is a clinically useful guide to the pace of phlebotomy therapy for hemochromatosis.

Massive immune haemolysis after allogeneic peripheral blood stem cell transplantation with minor ABO incompatibility.

Immune haemolysis as a result of minor ABO incompatibility is an underappreciated complication of haematopoietic transplantation. The increased lymphoid content of peripheral blood stem cell (PBSC) transplants may increase the incidence and severity of this event. We observed massive immune haemolysis in 3 out of 10 consecutive patients undergoing HLA-identical, related-donor PBSC transplants with minor ABO incompatibility. Non-ablative conditioning had been given in 9 of these 10 cases, including two with haemolysis. Cyclosporin alone was used as prophylaxis against graft-vs.-host disease (GVHD). Catastrophic haemolysis of 78% of the circulating red cell mass led to anoxic death in the first case seen, but severe consequences were avoided by early, vigorous donor-compatible red cell transfusions in the subsequent two cases. Haemolysis began 7-11 d after PBSC infusion and all patients with haemolysis had a positive direct antiglobulin test (DAT), with eluate reactivity against the relevant recipient antigen. However, neither the intensity of the DAT, the donor isohaemagglutinin titre, nor other factors could reliably be used to predict the occurrence of haemolysis. Our data indicate that haemolysis may be frequent and severe after transplantation of minor ABO-incompatible PBSCs when utilizing cyclosporin alone to prevent GVHD. Meticulous clinical monitoring and early, vigorous donor-compatible red cell transfusions should be practiced in all instances.

Operational medicine experience integrated into a military internal medicine residency curriculum.

The optimal training of physicians should prepare them for the environment in which they will practice. During the past several years, the practice of internal medicine has shifted from a focus on the inpatient setting to one that includes an emphasis on the ambulatory clinic. Military internists must be further prepared to practice medicine with forward units, at field hospitals, and in other operational settings. Community-based teaching programs that reflect present and future practice are increasingly recognized as essential, yet details on the structure and implementation of such programs, especially those designed to teach field and operational medicine, are lacking. The Internal Medicine Residency Program at Walter Reed Army Medical Center has developed and implemented an operational medicine curriculum that includes a field medical training exercise. The program is driven by the residents and chief resident and requires little additional funding. Resident research continues to increase, morale remains high, and the first class to complete the 3-year operational curriculum achieved a 100% pass rate on the American Board of Internal Medicine certification examination. We describe our 3-year experience of implementing this program, with an emphasis on curriculum design and execution, qualitative assessment, and initial lessons learned.

Intravenous Rh immune globulin prevents alloimmunization in D- granulocyte recipients but obscures the detection of an allo-anti-K.

Rh immune globulin (RhIG) has been used to prevent alloimmunization in D(-) recipients of apheresis platelet transfusions from D(+) donors that may contain up to 5 mL of D(+) red blood cells (RBCs). Granulocyte concentrates contain approximately 30 mL of RBCs and it has been necessary to give D(-) recipients granulocyte transfusions from D(+) donors. Intravenous RhIG has not yet been demonstrated to be effective in preventing D alloimmunization with granulocyte transfusions. Four D(-) recipients received multiple D(+) granulocyte transfusions from D(+) donors and multiple injections of intravenous RhIG at a standard dose of 600 microg for each D(+) transfusion. Two D(-) males with chronic granulomatous disease were given 32 and 13 daily granulocyte transfusions, 18 and 2 of which, respectively, were D(+). After the first dose of intravenous RhIG, both patients exhibited circulating anti-D that was undetectable 3 to 4 years later. Two patients with severe aplastic anemia were given 5 and 14 granulocyte transfusions, 4 and 7 of which, respectively, were D(+). Both patients died before the effectiveness of RhIG could be assessed. In one of these patients the indirect and direct antiglobulin tests became positive after the first dose of intravenous RhIG, which required that subsequent granulocyte transfusions from D(+) donors be crossmatched by immediate spin (IS) testing only. A delayed hemolytic reaction attributed to allo-anti-K occurred after granulocytes from a K(+) donor were given to this patient. These results suggest that intravenous RhIG can be used to prevent alloimmunization to D in D(-) patients receiving large quantities of RBCs from D(+) granulocyte transfusions. However, anti-D and other passive antibodies from RhIG prohibit the use of the antiglobulin crossmatch with antigen-positive granulocyte donor samples. It may be important to frequently collect new samples to screen for newly formed allo-antibodies when IS crossmatches are used in place of the antiglobulin crossmatch.

Operational experiences during medical residency: perspectives from the Walter Reed Army Medical Center Department of Medicine.

The preparation of military primary care physicians for practice in operational environments has taken on greater importance during the past decade. The Department of Defense military-unique curriculum identifies the elements that should be incorporated into residency training programs to accomplish comprehensive training in operational matters. We describe efforts to integrate the military-unique curriculum into internal medicine residency, including obstacles encountered, so that other programs may learn from our experience.

How often do high school guidance counselors suggest practical nursing as a career option?

The Centre for Nursing Studies provides practical nursing education in Newfoundland and Labrador. Because applications to the program from direct high school students were consistently low, in 1999 the Centre for Nursing Studies surveyed the provincial high school guidance counselors to determine their perceived knowledge level of the roles and responsibilities of Licensed Practical Nurses and the practical nursing program, the number of times they suggested practical nursing to students and characteristics they believed to be necessary for a practical nurse. There were 168 questionnaires distributed. Fifty (30%) returned questionnaires were analyzed. The results demonstrated that the majority of guidance counselors (66%) receive between 1 to 5 requests for information regarding practical nursing annually. Forty-eight percent suggest practical nursing as a career option 1 to 5 times annually, while an additional 22% suggest it 6 to 10 times. Some of the characteristics identified, by the guidance counselors, to be necessary for practical nurses include good people skills, empathy, hard working, good communication skills, a desire to help others and an interest in health care.

CD56 expression in acute promyelocytic leukemia: a possible indicator of poor treatment outcome?

PURPOSE: Blast expression of CD56 is frequent in patients with t(8;21)(q22;q22) acute myeloid leukemia and is associated with an inferior outcome. The expression of CD56 has rarely been reported in acute promyelocytic leukemia (APL) and has not been clinically characterized. Therefore, we examined the prognostic significance of CD56 expression in APL. PATIENTS AND METHODS: We identified all reported cases of CD56+ APL in the medical literature and collected clinical, biologic, and therapeutic details. RESULTS: Data were obtained for 12 patients with CD56+ APL (> 20% blast expression of CD56), including four cases from a single institution with a total of 42 APL patients. All of the CD56+ APL patients had documented cytogenetic presence of t(15;17), and of the nine reported isotypes, eight (89%) were S-isoform. Only six CD56+ patients (50%) attained complete remission (CR); the other six individuals died within 35 days of presentation. Of the six patients who attained a CR, three (50%) relapsed at 111, 121, and 155 weeks, whereas three remained in continuous CR at 19, 90, and 109 weeks. Comparison of the control CD56- to CD56+ APL patients demonstrated that the latter group had a significantly lower fibrinogen level (P = .007), and among patients for whom data were available, there was a higher frequency of the S-isoform (P = .006). Additionally, the CR rate (50% v 84%, P = .025) and overall median survival (5 v 232 weeks; P = .019) were significantly inferior for CD56+ APL patients. CONCLUSION: CD56+ acute promyelocytic leukemia is infrequent, seems to occur more frequently with the S-isoform subtype, and may be associated with a lower CR rate and inferior overall survival.

Role of plasminogen activator inhibitor-1 in promoting fibrin deposition in rabbits infused with ancrod or thrombin.

The role of defective fibrinolysis caused by elevated activity of plasminogen activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been well established. The present study compared the efficacy of thrombin or ancrod, a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour infusion of ancrod or thrombin; another set of normal rabbits received intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6). Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and in only 1 of 6 receiving rPAI-1 and thrombin (P < .01). In vitro, thrombin but not ancrod was inactivated by normal rabbit plasma and by purified antithrombin III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote fibrin deposition in rabbits infused with ancrod but not with thrombin. In endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion may be caused by decreased inhibition of procoagulant activity and not increased PAI-1 activity.

Association of protein S deficiency with thrombosis in a kindred with increased levels of plasminogen activator inhibitor-1.

OBJECTIVE: A single kindred in North America with venous thrombosis was described as having defective fibrinolysis because of increased levels of plasminogen activator inhibitor-1 (PAI-1). Our study describes the discovery of protein S deficiency in this kindred and its association with venous thromboembolism. DESIGN: A family study. SETTING: Community. PARTICIPANTS: Twenty-eight adults (ages 21 to 71 years) from three generations of the kindred; seven had a history of venous thromboembolism. MEASUREMENTS: Plasma levels of total and free protein S antigen, as well as the activities of protein S, protein C, PAI-1, and antithrombin III. RESULTS: Six of 7 persons (86%) with a history of venous thromboembolism were deficient in total and free protein S; of 21 asymptomatic members, 9 were deficient in protein S (P = 0.08). When compared with these 9 asymptomatic family members, the 6 persons with protein S deficiency and a history of thrombosis tended to smoke (P = 0.01) and to have higher triglyceride levels (P = 0.001). Overall, the mean PAI-1 activity in the 7 persons who had thrombosis was 7.9 kAU/L (AU/mL) and was 9.3 kAU/L (AU/mL) in the 21 persons who did not have thrombosis (95% CI, -9.9 to 7.0). CONCLUSIONS: In this kindred, a deficiency of total and free or functional protein S is the cause of thrombosis. Measurement of PAI-1 activity was not useful in the evaluation of familial thrombosis. The utility of the routine measurement of PAI-1 activity in the evaluation of familial thrombosis has not been established.

Human ehrlichiosis: a newly recognized tick-borne disease.

Human ehrlichiosis was first described in the United States in 1986. Since then, more than 215 cases have been reported, including some fatalities. Ehrlichia species belong to the same family as the organism that causes Rocky Mountain spotted fever. Human ehrlichiosis occurs most frequently in the southern mid-Atlantic and south-central states, during spring and summer months. The clinical presentation is similar to that seen in Rocky Mountain spotted fever although, with ehrlichiosis, leukopenia is more often found and skin rash is less often noted. Definitive diagnosis is based on acute and convalescent serum antibody titers. Ehrlichiosis cannot reliably be distinguished from other common febrile illnesses on the basis of clinical, epidemiologic or laboratory features. Therapy must be initiated empirically in suspected cases. Both ehrlichiosis and Rocky Mountain spotted fever respond well to tetracycline and chloramphenicol, but not to penicillins or cephalosporins.