Interferon alfa-2a maintenance after salvage autologous stem cell transplantation in atypical mycosis fungoides with central nervous system involvement.

Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma with unfavourable prognosis for patients with advanced stages of the disease. Refractory disease and advanced-stage disease require systemic therapy. We report on a rare case of an atypical predominantly CD8+ folliculotropic MF, a subtype of MF with poorer prognosis, in a 59-year-old woman. She was initially diagnosed with MF restricted to the skin, of T3N0M0B0/stage IIB according to the current World Health Organization-European Organisation for Research and Treatment of Cancer classification. First-line treatment with local percutaneous radiotherapy in combination with systemic interferon alfa-2a resulted in complete remission. However, 21 months later the disease progressed to T3N0M1B0/stage IVB with development of cerebral manifestation and thus very poor prognosis. Allogeneic stem cell transplantation (SCT) was not a therapeutic option due to the lack of a suitable donor. We initiated methotrexate and cytarabine chemotherapy, followed by high-dose chemotherapy with thiotepa and carmustine with autologous SCT. Despite rapid response and complete remission of the cerebral lesions, disease recurrence of the skin occurred soon after. Interestingly, readministration of interferon alfa-2a as a maintenance treatment after the salvage autologous SCT resulted in a durable complete remission during the follow-up period of currently 17 months after autologous SCT. What's already known about this topic? Mycosis fungoides is a primary cutaneous T-cell lymphoma with unfavourable prognosis for the advanced stages of the disease. A refractory course of disease requires systemic therapy. What does this study add? We report on an unusual case of a patient with mycosis fungoides with cerebral involvement, in which a durable complete remission was achieved upon autologous stem cell therapy and interferon alfa-2a maintenance therapy.

COVID-19 Pandemic Impact on US Childhood Caries and Potential Mitigation.

Non-Hispanic Black (NHB) and Hispanic and low-income US children have a higher prevalence of untreated caries than their higher-income and non-Hispanic White (NHW) counterparts. Due to the COVID-19 pandemic, many dental offices and school sealant programs closed beginning March 2020. We examine the effect of reduced access to restorative care and sealants on the oral health of children from low-income households overall and by race/ethnicity and how increased sealant delivery in September 2022 could mitigate these effects. We used Markov chain Monte Carlo simulation to model COVID-19's impact on first permanent molar (1M) caries incidence and loss in quality of life (disability-adjusted life years [DALYs]) due to time lived with 1M untreated caries. Our model followed a cohort of children aged 7 y in March 2020 until February 2024. Model inputs were primarily obtained from published studies and nationally representative data. Excess DALYs per 1,000 children attributable to reduced access to care during the pandemic were 1.48 overall and greater for Hispanic (2.07) and NHB (1.75) children than for NHW children (0.94). Excess incidence of 1M caries over 4 y was 2.28 percentage points overall and greater for Hispanic (2.63) and NHB (2.40) children than for NHW (1.96) children. Delivering sealants to 50% of eligible 1Ms in September 2022 would not completely mitigate COVID-19's health access impact: overall excess DALYs would decrease to 1.05, and absolute disparities in excess DALYs between NHW children and Hispanic and NHB children would remain but decrease by 0.38 and 0.33, respectively. Sealing 40% of eligible 1Ms, however, would bring overall 4-y caries incidence down to pre-COVID-19 levels and eliminate the differential effect of the pandemic on children from minority groups. The pandemic's negative impact on the oral health of children from low-income households and increased disparities could be partially mitigated with increased sealant delivery.

Expansion of cytokine-producing CD4-CD8- T cells associated with abnormal Fas expression and hypereosinophilia.

The mechanisms of sustained overproduction of eosinophils in the idiopathic hypereosinophilic syndrome and in some human immunodeficiency virus (HIV)-1-infected individuals are largely unknown. We hypothesized that T cells may release soluble products that regulate eosinophilia in these patients, as has been previously shown in bronchial asthma. We identified one patient with idiopathic hypereosinophilic syndrome and one HIV-1-infected individual with associated hypereosinophilia who demonstrated high numbers of CD4-CD8- T cells in peripheral blood. CD4-CD8- T cells from both patients, although highly activated, did not express functional Fas receptors. In one case, the lack of functional Fas receptors was associated with failure of Fas mRNA and protein expression, and in another, expression of a soluble form of the Fas molecule that may have antagonized normal signaling of Fas ligand. In contrast to the recently described lymphoproliferative/autoimmune syndrome, which is characterized by accumulation of CD4-CD8- T cells and mutations within the Fas gene, this study suggests somatic variations in Fas expression and function quite late in life. Both genetic and somatic abnormalities in regulation of the Fas gene are therefore associated with failures to undergo T cell apoptosis. Furthermore, the expanded population of CD4-CD8- T cells from both patients elaborated cytokines with antiapoptotic properties for eosinophils, indicating a major role of these T cells in the development of eosinophilia. Thus, this study demonstrates a sequential dysregulation of apoptosis in different cell types.

MAGE-C1/CT-7 expression in plasma cell myeloma: sub-cellular localization impacts on clinical outcome.

Plasma cell myelomas (PMs) have a poor prognosis. Cancer-testis (CT) antigens are immunogenic proteins, representing potential targets for tumor vaccination strategies. The expression of the CT antigens GAGE, MAGE-A4, MAGE-C1/CT-7, and NY-ESO-1 was investigated on paraffin-embedded bone marrow biopsies from 219 PM and 8 monoclonal gammopathy of undetermined significance (MGUS) patients. The frequency and prognostic impact of these CT antigens were compared with known morphological prognostic markers (i.e. Mib1 labeling index) and the presence of the translocations t(4;14)(p16.3; q32) and t(11;14)(q13;q32). We show that MAGE-C1/CT-7 is the most prevalent CT antigen, expressed in 57% of PMs in a high percentage of tumor cells. While MAGE-C1/CT-7 was absent in non-malignant plasma cells, plasma cells of patients with MGUS did express MAGE-C1/CT-7, but no other CT antigens. MAGE-C1/CT-7 was more frequently expressed in PMs with an elevated proliferation rate (Mib1 >10%) compared to PMs with a low proliferation rate (Mib1

[Prevalence of Brugada syndrome among 35,309 inhabitants of Lorraine screened at a preventive medicine centre]. / Prevalence du syndrome de Brugada dans une population de médecine préventive en Lorraine a propos de 35,309 cas.

UNLABELLED: Brugada syndrome is a recently identified cause of sudden death. Its primary prevention remains controversial, and epidemiology poorly defined. PATIENT POPULATION AND METHODS: Electrocardiograms (ECG) of 35,309 individuals (mean age = 37.2 years, 47% men) recorded over a 1-year period were reviewed and classified as (1) typical, (2) suspicious, and (3) negative. Subjects whose ECG was suspicious were offered a provocative test with flecainide, 2 mg/kg, i.v., and individuals whose ECG was typical were advised to undergo programmed ventricular stimulation (PVS). RESULTS: In 14 men and 6 women between the ages of 24 and 77 years (mean =47.5), ECGs were typical (n=6) or suspicious (n=14). Among 6 subjects with typical ECGs, 3 underwent PVS, which was positive in 1, who received an implantable cardioverter defibrillator (ICD). Among 14 subjects whose ECGs were suspicious, 5 declined further investigations and 5 developed typical ECG characteristics of Brugada syndrome after flecainide administration. PVS was negative in 4 subjects who consented to the procedure. Overall, among 35,309 individuals screened, 11 had ECG findings consistent with Brugada syndrome and, over a follow-up of 30 months, all had remained free of adverse cardiac event. CONCLUSIONS: we estimated a prevalence of Brugada syndrome of 0.3% in Lorraine. A single patient received an ICD for inducible ventricular tachyarrhythmia during PVS, representing a potential 30 per million asymptomatic adult rate of ICD implantation for this indication.

Occult hepatosplenic T-gamma delta lymphoma. Value of genotypic analysis in the differential diagnosis.

We report on a patient with a rare hepatosplenic gamma delta T-cell lymphoma (gamma delta TCL) presenting clinically with B-symptoms, hepatosplenomegaly and pancytopenia. During the initial stage of the disease the sparse malignant cells could not be detected histologically. Furthermore, their identification was obscured by massive macrophage proliferation with haemophagocytosis in the spleen. Diagnosis was established by detection of a clonal T-cell receptor (TcR) rearrangement and, retrospectively, by demonstration of rare cells expressing and aberrant T-cell phenotype. The findings in this patient emphasize that minimal neoplastic T-cell infiltrates can lead to severe clinical symptoms. Initial biopsy findings may be misinterpreted as benign. Gamma delta TCL may elaborate lymphokines that suppress haematopoiesis, leading to pancytopenia and macrophage proliferation.

Long-term outcome of idiopathic hypereosinophilic syndrome--transition to eosinophilic gastroenteritis and clonal expansion of T-cells.

We describe a patient with idiopathic hypereosinophilic syndrome, without initial gastrointestinal symptoms, and their transition to eosinophilic gastroenteritis. This patient, a 65-year-old man, presented with fever, constitutional symptoms, peripheral and bone marrow eosinophilia 20 years ago. During the course of the disease, diarrhoea and malabsorption became prominent, whereas bone marrow eosinophilia regressed completely and blood eosinophilia regressed partially. Biopsies showed a severe eosinophilic gastroenteritis of the mucosal type involving the stomach, small bowel and colon. During the final years of the patient's disease, mucosal eosinophilia became less intense and a mucosal infiltration with T-cells dominated. At autopsy, immunopathological studies of small intestines and colon specimens showed a clonal expansion of morphologically normal T-cells in the intestinal mucosa, which expressed the abnormal phenotype CD2+CD3+CD4-CD5-CD8-. Flow cytometry examination of peripheral blood revealed a corresponding abnormal population of CD3+CD4-CD8- T-cells, indicating a systemic spread of the process. The patient eventually died of non-obstructive small bowel infarction with peritonitis 20 years after the onset of the first symptoms. We postulate that the destructive eosinophilic/lymphocytic inflammation is caused by a clonal proliferation of T-lymphocytes with probable secretion of Type 2 T(helper) cell cytokines and consecutive stimulation of eosinophils.

Clonal disease in extracutaneous compartments in cutaneous T-cell lymphomas. A comparative study between cutaneous T-cell lymphomas and pseudo lymphomas.

Extracutaneous involvement is a sign of poor prognosis in cutaneous T-cell lymphomas (CTCL). Unfortunately it becomes clinically and histologically manifest only late in the course of the disease. It was the purpose of this study to detect clonality in peripheral blood, lymph nodes and bone marrow samples at times when extracutaneous involvement cannot otherwise be demonstrated. In addition to skin biopsies, peripheral blood, lymph node and bone marrow samples from a total of 25 patients were analysed by Southern blotting for clonal gene rearrangement of the T-cell receptor beta-chain. Six of the patients were suffering from mycosis fungoides (MF), four from non-MF CTCL (pleomorphic T-cell lymphomas), seven from Sézary syndrome (SS), eight from pseudolymphoma (insect bites) (PSL), and one from lymphomatoid papulosis (LP). Clonal TcR b gene rearrangements were found in patients with MF in four of five skin probes as well as in two of two lymph node samples and in one of two peripheral blood samples. In SS patients, all skin probes (seven of seven), lymph node samples (six of six), peripheral blood samples (six of six) and one bone marrow specimen had a clonal TcR beta gene rearrangement. In patients with non-MF CTCL, two of four skin, zero of two peripheral blood and one of one bone marrow samples with clonal T cells were detected. All investigated patients showed exactly the same rearrangement pattern at extranodal sites and in the skin, which is proof for the same clone in all compartments. In contrast, no rearrangements were detected in LP and PSL (zero of eight skin probes, zero of two peripheral blood samples). Our results provide strong evidence for an early systemic spread of neoplastic cells in CTCL. However, an initial tumour burden has to be reached in order to lead to a clinically and prognostically relevant manifestation.

Inflammatory aneurysm of the splenic artery.

The case of a middle-aged man is described, who was admitted because of intermittent back pain and a high sedimentation rate. Abdominal sonography and arteriography showed a large aneurysm of the splenic artery, but failed to recognize the aneurysm as of inflammatory origin. However, the inflammatory nature of the aneurysm was evident on computer tomography scan. Intraoperatively the inflammatory origin of the aneurysm was confirmed. A saphenous vein graft was implanted and marsupialization of the aneurysm performed. Histology could clearly verify the diagnosis of an inflammatory aneurysm. This report indicates the possibility of inflammatory changes occurring in connection with a visceral artery rather than solely with the abdominal aorta.

[Vascular sinus transformation of the lymph nodes. Morphological and immunohistochemical analysis of 6 cases]. / La transformation vasculaire sinusienne du ganglion lymphatique. Analyse morphologique et immunohistochimique de six cas.

Vascular sinus transformation (VST) of lymph nodes is characterized by the intrasinusoidal proliferation of endothelial cells forming a system of anastomosed channels filled with blood, and by an intrasinusoidal fibrous reaction. By analysis of six cases, the authors recall the histological criteria of this rare lesion and discuss its differential diagnosis. The endothelial nature of the proliferating cells is demonstrated by the presence of factor VIII related antigen. VST is usually observed in association with a thrombosis of lymph node veins. On the basis of their observations the authors suggest that a venous congestion only, accompanied by lymph congestion of lymph flow may induce a VST.

[Post-laparoscopic incisional hernia. Apropos of a case]. / Les hernies incisionnelles post-coelioscopiques. A propos d'un cas.

Incisional hernia occurred in a patient after laparoscopic hysterectomy. The greater omentum was incarcerated in the tract of the suprapubic trocar (12 mm diameter). Diagnosis and treatment were performed during a second laparoscopy procedure. The greater number of trocar instruments and their larger diameter increases the risk of parietal morbidity after laparoscopic procedures. Elective closures of trocar incisions is recommended when exceeding 10 mm. Prevention of extra-umbilical incisional hernias and dehiscences appears to be more effective when suture is performed under laparoscopic vision with the trocar inserted. Both the aponevrosis and the peritoneal membrane should be treated.

The evolving role of the librarian in evidence-based medicine.

Librarians' participation in evidence-based medicine (EBM) is rooted in past practices, most notably in clinical medical librarianship. EBM extends the librarians' role beyond identification of the literature to involvement in practicing and teaching quality filtering and critical appraisal of the literature. These activities require librarians to acquire new knowledge and develop new skills. A professional development program for librarians at the Library of the Health Sciences (LHS) at the University of Illinois at Chicago (UIC) is described. The program's goals are to increase librarians' skills and support the EBM curricular initiative at the UIC College of Medicine (COM). The unique program has been a collaborative effort of the LHS and the COM. The locally developed classes provide librarians with instruction in clinical study designs, statistical concepts, and critical appraisal of the literature. Other interventions such as an EBM round table are also described. The programs' success is measured by librarians' growing involvement in EBM medical curricula, journal clubs, and morning reports. Additionally, librarians gained competence in new skills and professional satisfaction from working collegially with COM students, residents, and faculty.

Tools for improvement: a systematic analysis and guide to accreditation by the JCAHO.

By viewing the Joint Commission on Accreditation of Healthcare Organizations' (JCAHO) standards in the context of current accreditation practice, hospital librarians can understand and clarify their role in realizing their organization's mission, goals, and objectives. By broadening their view of the information function as described in the accreditation standards, health sciences librarians can enhance their position in the hospital's management team, improve health information practice, and contribute to the overall performance of the health care organization. The role of the librarian and the library throughout the entire set of standards and interrelationships with other professionals and units are described. Examples of ways to demonstrate conformity to the standards are provide. Special emphasis is placed on Standard 9, Management of Information, to provide guidance to the librarian undergoing JCAHO accreditation.

Brain stem and cervical cord dysraphic lesions in iniencephaly.

Iniencephaly is a rare, lethal, axial dysraphic malformation complex diagnosed on the basis of three cardinal features: deficiency of the occipital bone, cervicothoracic spinal retroflexion, and rachischisis. The majority of the patients also have various associated viscerae malformations. An iniencephalic female fetus delivered at 35 5/7 weeks of gestation revealed severe anomalies of the central nervous system and the spine: the cerebellar vermis was hypoplastic, the medulla oblongata was flattened and broadened, and the cervical canal was widely patent dorsally. The thoracolumbar spinal cord had a duplicated central canal and lacked a dorsal fissure, representing a minor degree of diastematomyelia. The cervicothoracic spine showed severe bony anomalies including aplasia and fusion of vertebral bodies.

[Well-differentiated papillary mesothelioma of the peritoneum. Rare, but prognostically important differential diagnosis]. / Gut differenziertes papilläres Mesotheliom des Peritoneums. Rarität, aber prognostisch wichtige Differentialdiagnose.

A 35-year-old man who presented with ascites and multiple small peritoneal nodules is still in good health after a follow-up of 6 years despite the fact that two different former histologic sections were interpreted as malignant mesothelioma. The present histologic finding is a well differentiated papillary mesothelioma. We review the literature and discuss the significance of this uncommon finding. It is generally associated with an excellent prognosis. Chemotherapy should be withheld.

[Iniencephaly: prenatal and postnatal findings]. / Inienzephalie: Pränatale und postnatale Befunde.

A 33-year-old para-3 was admitted in the 33rd week of gestation because of a suspected foetal anomaly. Ultrasound examination showed polyhydramnios, exaggerated cervico-thoracic lordosis and significant shortening of the spine because of a reduced number of vertebrae. The facial profile was flat, the foetal movements were rare and slow, and the extremities normal. A biopsy of the placenta revealed a normal female karyotype. Based on ultrasound examination, the diagnosis of iniencephaly was made. Because of the fatal prognosis of this malformation, labour was induced at 35 weeks of gestation. The patient delivered spontaneously. The infant died after 90 minutes. The postmortem examination confirmed the diagnosis of iniencephaly. Iniencephaly is a very rare malformation comprising a bone defect at the occiput, malformation of the cervical and thoracic vertebrae, spina bifida, and retroflexion of the head. The aetiology is not clear. 90% of the probands are female. The malformation is incompatible with survival after birth.

[Proximo-distal course of the diameter of the great saphenous vein and distribution of the number of side branches as an inherent difficulty in infra-inguinal arterial in situ bypass]. / Der proximo-distale Verlauf des Durchmessers der V. saphena magna und die Häufigkeitsverteilung der Seitenäste als inhärente Schwierigkeit des infrainguinalen arteriellen In-situ-Bypasses.

The greater saphenous vein is still the best material for infrainguinal arterial bypasses, particularly if they have an infrapopliteal distal anastomosis. Although a lot of advantages have been presumed for the in-situ bypass, the reported results are not significantly better than with the reversed technique. To find some additional explanations, we studied post mortem the anatomy of 20 greater saphenous veins with regard to the diameter and the number of side branches and compared the results with 10 phlebographies. A minimal diameter (2.6 mm) and a maximum of side branches and venous valves were found at the proximal calf. Furthermore, this region was characterized by a lot of anatomic variants such as double systems (25%) or cross over variants (5%). These findings are surgically relevant and may reduce the bypass patency: 1. There is an increased hemodynamic resistance in longer bypasses, 2. The small diameter (particularly if smaller than 2 mm) means a risk for the patency of the distal anastomosis, 3. The high frequency of side branches requires a comparable exposition of the GSV as for the reversed technique, 4. The introduction of the valvulotomy from distally may overestimate the proximal diameter and underestimate the frequency of variants and may therefore cause significant endothelial damages or even perforation.

[Revascularization of tracheal transplants with omentum]. / Revaskularisierung von Tracheatransplantaten durch das Omentum.

UNLABELLED: In a series of 6 dogs we performed an autotransplantation of a four-ring segment of the thoracic trachea. In 3 cases the omentum was brought into the chest and wrapped around the transplant (omentum group) and compared with the others (control group). After 20 days or at occurrence of severe tracheal stenosis the study was determined. In the omentum group all tracheal transplants healed with structural integrity. Microfil injection into the gastro-epiploic artery demonstrated revascularization through omental vessels. In the control group all transplants developed a severe stenosis due to chondromalacia within 2 weeks. IN CONCLUSION: The omentum can successfully revascularize a transplant of a four-ring segment of the thoracic trachea.

[Pattern of intermediate filaments in thymomas]. / Intermediärfilamentmuster von Thymomen.

The cytokeratin pattern of medullary, mixed and cortical thymomas and thymic carcinomas were analyzed by two-dimensional equilibrium electrophoresis. Extracts from a medullary thymoma and normal, total thymi showed a similar pattern. On the other hand in cortical thymomas and very similar in thymic carcinomas there were marked changes in the cytokeratin pattern. These findings support the classification of thymomas as described by MULLER-HERMELINK.