First case of chronic post-traumatic anterior pituitary dysfunction in a professional rugby player: A case report.

BACKGROUND: Post-traumatic hypopituitarism has been reported as a complication in a number of contact sports. Although rugby is a sport with a high risk and high incidence of concussion, no such cases have been reported to date. CASE PRESENTATION: A 35-year-old professional rugby player presented with fatigue and reduced libido complaints after nearly 300 professional games during his 15-year career. At the end of the season, biological monitoring was performed and revealed low total testosterone level associated with a low luteinizing hormone, suggestive of central hypogonadism. Brain magnetic resonance imaging (MRI) revealed the presence of a 10-mm sequel lesion in the right medial temporal lobe and two additional punctiform lesions, all suggestive of post-traumatic brain injury lesions. Testosterone replacement therapy was initiated and the player perceived an overall decrease in fatigue and complete restoration of his libido after only a couple of weeks of treatment. During follow-up, thyrotropic deficiency was diagnosed 2 years after initial diagnosis treated by l-Thyroxin. CONCLUSIONS: In conclusion, this case report highlights a new post-traumatic brain injury complication in a professional rugby player, namely chronic post-traumatic anterior pituitary dysfunction. STUDY DESIGN: Case report; level of evidence 4.

Acute Kidney Injury Following High-Dose Methotrexate Administration in a Day Care Hospital.

Day care is a potential alternative to inpatient care of cancer patients. Using day care reduces medical costs substantially compared to inpatient care, which is driving the transfer of many inpatient chemotherapy protocols to day care hospitals (DCHs). However, in contrast to inpatient management, day care provides limited observation time, which could increase the risk of renal toxicity when using these protocols. We present a case report of acute kidney injury following high-dose methotrexate administration in a DCH. Based on a review of the current literature on acid-base balance, we also discuss appropriate patient selection and judicious hydration and urine alkalinization so as to prevent toxicity in the day care setting.

Paroxysmal Nocturnal Hemoglobinuria with a Distinct Molecular Signature Diagnosed Ten Years after Allogenic Bone Marrow Transplantation for Acute Myeloid Leukemia.

Paroxysmal nocturnal hemoglobinurea (PNH) is a rare disorder of complement regulation due to somatic mutation of PIGA (phosphatidylinositol glycan anchor) gene. We herewith report a case who developed a symptomatic PNH long after an allogenic marrow transplant. Some reasonable arguments concerning the origin of PNH clone have been discussed. The molecular studies revealed presence of JAK2 and TET2 mutations without a BCOR mutation. The literature review has been performed to probe into the complex interplay of autoimmunity and clonal selection and expansion of PNH cells, which occurs early in hematopoietic differentiation. The consequent events such as hypoplastic and/or hemato-oncologic features could further be explained on the basis of next-generation sequencing (NGS) studies. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder of hematopoietic stem cells, characterized by a somatic mutation of the phosphatidylinositol glycan-class A (PIGA). The PIGA gene products are crucial for biosynthesis of glycosylphosphatidylinositol (GPI) anchors, which attaches a number of proteins to the plasma membrane of the cell. Amongst these proteins, the CD55 and CD59 are complement regulatory proteins. The CD55 inhibits C3 convertase whereas the CD59 blocks the membrane attack complex (MAC) by inhibiting the incorporation of C9 to MAC. The loss of complement regulatory protein renders the red cell susceptible to complement-mediated lysis leading to intravascular and extravascular hemolysis. The intravascular hemolysis explains most of the morbid clinical manifestations of the disease. The clinical features of syndrome of PNH are recurrent hemolytic episodes, thrombosis, smooth muscle dystonia, and bone marrow failure; other important complications include renal failure, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML). The most used therapies were blood transfusions, immunosuppressive, and steroid. Allogeneic stem cell transplantation was also practiced. At present, the therapy of choice is eculizumab (Soliris, Alexion Pharmaceuticals), a humanized monoclonal antibody that blocks activation of the terminal complement at C5. The limiting factor for this therapy is breakthrough hemolysis and the frequent dosing schedule. Ravulizumab (ALXN1210) is the second generation terminal compliment inhibitor which seems to provide a sustained control of hemolysis without breakthrough hemolysis and with a longer dosing interval.

Workload, Fatigue, and Muscle Damage in an Under-20 Rugby Union Team Over an Intensified International Tournament.

PURPOSE: To examine the effects of an intensified tournament on workload, perceptual and neuromuscular fatigue, and muscle-damage responses in an international under-20 rugby union team. METHODS: Players were subdivided into a high-exposure group (HEG, n = 13) and a low-exposure group (LEG, n = 11) according to match-play exposure time. Measures monitored over the 19-d period included training session (n = 10) and match (n = 5) workload determined via global positioning systems and session rating of perceived exertion. Well-being scores, countermovement jump height performance, and blood creatine kinase concentrations were collected at various time points. RESULTS: Analysis of workload cumulated across the tournament entirety for training and match play combined showed that high-speed running distance was similar between groups, while a very likely larger session rating of perceived exertion load was reported in HEG vs LEG. In HEG, high-speed activity fluctuated across the 5 successive matches, albeit with no clear trend for a progressive decrease. No clear tendency for a progressive decrease in well-being scores prior to or following matches was observed in either group. In HEG, trivial to possibly small reductions in postmatch countermovement jump performance were observed, while unclear to most likely moderate increases in prematch blood creatine kinase concentrations occurred until prior to match 4. CONCLUSIONS: The magnitude of match-to-match changes in external workload, perceptual and neuromuscular fatigue, and muscle damage was generally unclear or small. These results suggest that irrespective of exposure time to match play players generally maintained performance and readiness to play across the intensified tournament. These findings support the need for holistic systematic player-monitoring programs.

Chronic sinusitis in a patient with selective IgG4 subclass deficiency controlled with enriched immunoglobulins.

A 71-year-old female patient with no major history of infection had presented with recurrent chronic purulent sinusitis over the past 3 years. These recurrent infections started in 2000 with otolaryngologists' support before diagnosis of IgG4 deficiency be asked. The patient was treated with increasingly extensive courses of antibiotics and underwent several maxillary and sphenoidal sinus washouts. She continued to present with purulent nasal discharge containing Staphylococcus epidermidis. The blood and immune work-ups were normal. Her antinuclear antibody count was 1/320, with no unusual types. The total immunoglobulin (Ig)E, serology, CD4 count, and lymphocyte B phenotype results were all normal. No humoral immune deficiency was detected. The analyses confirmed an underlying specific IgG4 deficiency with values of 3-4 mg/L over 4 months. The patient was treated in March 2011 with prophylactic antibiotic therapy, sinus drainage, and IV infusions of enriched immunoglobulins (IVIg 10%) administered at the outpatient clinic every 4 weeks for 3 months. The IgIV treatment was not interrupted. Her general condition improved within a few months, with her IgG4 levels rising to 44 mg/L. The IVIg infusions were well tolerated. The purulent nasal discharge was controlled, and the antibiotics were stopped. The follow-up visits at 2 and 9 months after introduction of IVIg showed that her IgG4 level had improved, rising to 15 and 11 mg/L, respectively, although it had not yet returned to normal. The infusions were then given every 3 weeks. At her last visit, the patient's clinical condition had substantially improved. She was able to start using the subcutaneous Ig concentrate form (20% SCIg), 15 g every 2 weeks, leading to a clear improvement in her clinical condition, with stabilization of her otolaryngologists' symptoms and signs. The complete blood count was normal, IgG4 were stable at 40 mg/L, and the other immunoglobulins and IgG subclasses were normal. It was then possible to reduce the SCIg dose to 10 g every 3 weeks, while continuing to monitor her clinical condition and laboratory test results. This is one of the rare cases of selective IgG4 subclass deficiency treated with immunoglobulins. Treatment resulted in a significant improvement in IgG4 levels versus pretreatment levels. The first improvement noted was the stabilization otolaryngologists' infections particularly purulent nasal discharge.

How to Diagnose Early 5-Azacytidine-Induced Pneumonitis: A Case Report.

Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m2 for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 °C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment.

Eighty percent of French sport winners in Olympic, World and Europeans competitions have mutations in the hemochromatosis HFE gene.

The HFE gene encodes a protein involved in iron homeostasis; individuals with mutations in both alleles develop hemochromatosis. 27% of the French population is heterozygous for mutations in this gene. We found that 80% of the French athletes who won international competitions in rowing, Nordic skiing and judo display mutations in one allele of HFE, thus demonstrating the existence of a favourable phenotype linked to this heterozygosity.

[Hereditary hemochromatosis, the clinician point of view]. / L'hémochromatose génétique, le point de vue du clinicien.

Hereditary hemochromatosis (HH) is an autosomal recessive disease whose most common form is due to homozygosity for the C282Y mutation of the HFE gene. Its prevalence is estimated between 1/200 and 1/600 in France. This represents potentially several thousands of affected people. The disease is characterized by progressive iron overload, which can lead to irreversible parenchymal tissue damage. When clinical signs become evocative the disease is already at an advanced stage and years of life are probably lost. It is therefore important to detect the disease early. The clinician, either general practitioner or specialist, plays a pivotal role in the diagnostic process: he/she receives complaints of patients, prescribes complementary investigations, conducts the treatment and must organize of the family screening. Based on the French recommendations and on literature data, this paper presents the main lines of management of the patient as responses to the eight following questions: 1) Under what circumstances should the clinician suspect HH? 2) How to conduct investigations in the presence of high ferritin levels? 3) What manifestations must be feared with the worsening of iron overload? 4) What medical evaluation should be performed when the diagnosis of HH has been made? 5) How to conduct iron depletive treatment in practice? 6) How to monitor the treated patient? 7) What is the place of iron-chelating drugs in the treatment of HH? 8) How to take charge of the family members?

Nuclear chromatin patterns in 3 glucocorticoid-resistant RPMI 8226 human myeloma cell sub-lines: correlations with cell growth and immunological phenotype.

Nuclear morphological alterations associated with glucocorticoid resistance in human myeloma were evaluated by image cytometry in three human myeloma RPMI 8226 cell sub-lines. Resistance was induced by drug selection using prednisone (8226p), methylprednisolone (8226m) and dexamethasone (8226d), respectively. All these three cell sub lines displayed significant glucocorticoid-resistance without cross-resistance to doxorubicin. Nuclear geometry and texture were analyzed on G0/G1-selected cell nuclei and data compared with cell growth characteristics and membrane expression of CD23, CD38, CD44 and CD58 antigens. When compared to the parental RPMI 8226 cell line, glucocorticoid-resistant cells display a progressive chromatin condensation with heterogeneously distributed large chromatin clumps, a phenomenon not observed in the multidrug-resistant CEM-VLB cells. These alterations were correlated to the resistance index against glucocorticoids and to the expressions of CD38, and of CD44 variant forms CD44v5 and CD44v7-8 antigens. These data suggest that glucocorticoid resistance in RPMI 8226 cells could be associated with sub-visual specific higher-order chromatin organization changes. Furthermore, these alterations are correlated to the expression of membrane markers associated with tumors aggressiveness.

Phenotypical alterations induced by glucocorticoids resistance in RPMI 8226 human myeloma cells.

Resistance to glucocorticoids (GCs) frequently appears during treatment of hematological malignancies. This study investigates the phenotypical alterations observed in human myeloma cell sublines resistant to glucocorticoids. Using the RPMI8226 cell line, the cytotoxic efficiencies of four glucocorticoids, and the phenotypes of isolated resistant sublines were analyzed. Methyl-prednisolone and dexamethasone exhibited the higher toxic effects on RPMI8226 cells. All corticoids were able to induce drug-resistance. Resistant sublines showed an increased expression of the alpha-isoform of the glucocorticoid receptors (GRs), and specific modulations in CD23, CD38, CD44 and CD58 expressions. Thus, glucocorticoid resistance in RPMI8226 cells is accompanied by significant phenotypical alterations that could be implicated in survival enhancement to therapy and/or tumor spreading.