Deficient IFNα production in hairy cell leukemia

Summary Since the application of low doses of IFN-alpha is necessary to maintain remissions in Hairy Cell Leukemia (HCL) it is of interest whether peripheral blood mononuclear cells (MNC) of HCL patients can be induced in vitro to produce IFN-alpha. 9 patients suffering from advanced HCL were included in the study. The diagnoses were confirmed by characteristic findings in peripheral blood and bone marrow biopsies. For IFN treatment we initially used natural IFN-alpha (Bioferon) and switched later to recombinant IFN-alpha₂ (Boehringer). MNC of 5 patients before IFN therapy and of 6 patients during IFN therapy (2–47 weeks) were induced by phythemagglutinin (PHA), Corynebacterium parvum (C.p.), and sendai virus (SV). PHA is known to induce IFN-gamma. Both, C.p. and SV induced IFN-alpha but no IFN-gamma in MNC of healthy controls and of IFN treated breast cancer patients. In HCL patients normal antiviral activities could be induced by PHA. Zero or only low antiviral activities could be induced in MNC from 9 patients tested on 22 occasions. It is concluded that MNC from patients with advanced HCL can be induced to produce IFN-gamma but no IFN-alpha. Since IFN-alpha but not IFN-gamma is produced by monocytes it is likely that reduced numbers of monocytes which were found in our HCL patients before and during IFN treatment account for the described deficiency of IFN-alpha production.     

Kidney biopsy in the elderly: diagnostic adequacy and yield

International Urology and Nephrology - The number of kidney biopsies (KB) performed in elderly patients has been increasing. Safety and usefulness of elderly KB have been well established, whereas...     

The prevalence of metabolic syndrome is increased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis

Purpose

Cardiovascular disease is one of the major causes of mortality in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Metabolic syndrome (MetS) is associated with increased cardiovascular risk in the normal population. However, MetS in AAV has not been adequately investigated. We aimed to determine MetS prevalence and associated factors in AAV patients.

Methods

Thirty-seven AAV patients and 42 healthy controls were enrolled. MetS was determined by International Diabetes Federation (IDF) and National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. The relationship between clinical features of AAV and MetS was also investigated.

Results

MetS was significantly higher in AAV patients than controls by NCEP-ATPIII (51.4% vs. 26.2%, p 0.022) and IDF (62.2% vs. 35.7%, p 0.020). When AAV patients with MetS were compared to those without, there were significant differences in age, CRP, GFR and NT-pro-BNP. Age [58 (13) vs. 50 (8) years p: 0.028], CRP [4.0 (3.6) vs. 3.2 (1.0) mg/l, p 0.021] and NT-pro-BNP [173.5 (343.7) vs. 106.0 (103.0) pg/ml, p 0.013] were significantly higher in AAV patients with MetS than those without; GFR was significantly lower [38 (46) vs. 83 (51) ml/min/1.73 m², p 0.004]. ROC curve analysis showed NT-pro-BNP?>?58.0 ng/ml predicted MetS with 87.1% sensitivity and 46.7% specificity (Area under curve: 0.71, CI 0.536–0.902, p 0.041). Multivariate analysis revealed age [OR (95% CI): 1.180 (1.010–1.370), p 0.039] and NT-pro-BNP?>?58 pg/ml [OR (95% CI): 5.5 (1.02–30.1) p 0.047] were independent predictors of MetS in AAV patients.

Conclusion

MetS is significantly higher in AAV patients than controls and is associated with age and NT-pro-BNP. Screening and treating MetS may improve prognosis in AAV patients.

     

Carbamazepine-induced sperm disorders can be associated with the altered expressions of testicular KCNJ11/miR-let-7a and spermatozoal CFTR/miR-27a

Male infertility is a global health problem, and the underlying molecular mechanisms are not clearly known. Ion channels and microRNAs (miRNAs), known to function in many vital functions in cells, have been shown to play a significant role in male infertility through changes in their expressions. The study aimed to evaluate the alterations of testicular and/or spermatozoal potassium voltage-gated channel subfamily J member 11 (KCNJ11), Cystic fibrosis transmembrane conductance regulator (CFTR), miR-let-7a and miR-27a expressions in carbamazepine-related male infertility. Here, we showed that carbamazepine reduced sperm motility, increased abnormal sperm morphology, and impaired hormonal balance as well as increased relative testis weight and decreased relative seminal vesicle weight. On the other hand, downregulated KCNJ11 and upregulated miR-let-7a expressions were determined in testis (p < .05). Also, downregulated KCNJ11 and upregulated CFTR and miR-27a expressions were found in spermatozoa (p < .05). Interestingly, altered testicular KCNJ11 and miR-let-7a expressions were correlated with decreased sperm motility and elevated sperm tail defect. Besides, spermatozoal CFTR and miR-27a expressions positively correlated with sperm tail defects. The results indicated a significant relationship between ion channel and/or miRNA expression alterations and impaired sperm parameters due to carbamazepine usage.     

Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.     

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.     

Development of myasthenia gravis after interferon alpha therapy

Interferon (IFN) alpha is now used in the treatment of some malignant diseases and chronic viral hepatitis. There have been several reports of development of autoantibodies and autoimmune diseases or the deterioration of preexisting disorders in patients under treatment. We enclose a case of myasthenia gravis (MG) which developed after six weeks of treatment as fluctuating bilateral ptosis, intermittent diplopia, and mild weakness of limb and neck muscles. A test dose of edrophonium chloride was administered, resulting in improved muscle strength. Elevated anti acetylcholine receptor (AChR) antibody titer was found. Single fiber electromyography showed an increased jitter from extensor digitorum communis, frequently accompanied by transmission blocking. Repetitive electric 3 Hz stimulation of the abductor pollicis brevis muscle, revealed an abnormal decrement of 28% in compound motor action potential. Myasthenia gravis was diagnosed and the patient was given pyridostigmine, immunoglobulines and prednisone with benefit. Six months latter he developed an acute myasthenic crisis with severe respiratory failure and high anti AChR antibody titer. IFN-alpha can induce MG or simply manifests a preexisting subclinical disease, but otherwise its therapeutic efficacy in MG has been shown in experimental and clinical studies. Autoimmune mechanisms, as the release of different cytokines as IFN, by immunocompetent cells, may be involved in the pathogenesis of both MG and chronic active hepatitis. Autoantibody production against postsynaptic membrane structures by IFN-alpha could be the underlying pathophysiology.     

Rhabdomyolysis in a medical student induced by body-building exercise (rhabdomyolysis following acute muscular exertion)]

A medical student sportsman had been admitted to the hospital because of weakness and painful swelling of the muscle as well as dark urine appearing after carrying out an excessive body-building performance. On the basis of indirect evidences pigmenturia "per exclusionem" was a manifestation of urinary myoglobin excretion. The development of an "acute exertional rhabdomyolysis" was confirmed by the increased serum enzyme levels and myoglobinuria. The outcome of the illness was fortunate, as acute renal failure could be avoided. On the basis of survey of the literature it can be stated, that this presumably frequently occurring, but rarely recognized disease may have importance from clinical, sporting medicine and pathophysiological point of view.     

Coagulase-negative staphylococci and sternal infections after cardiac operation

BACKGROUND: Coagulase negative staphylococci (CoNS) have been recognized as important pathogens in nosocomial infections, especially in connection with implanted foreign materials. In cardiac operation they are among the most common pathogens isolated from infected sternal wounds. The definition of the infection is very important. In this study we focus on deep postoperative chest infections. METHODS: By studying 33 infected patients retrospectively and comparing them to 33 matched uninfected controls, we studied the characteristics and costs of the infections. RESULTS: Typical for these infections is the late and insidious onset, and that the infections initially give only minor symptoms such as pain, redness, and serous secretion. We found the following risk factors for infection: number of preoperative days in a hospital, the total length of the operation, and if the patient had undergone an early reoperation due to causes other than infection. This kind of infection more than doubled the hospital costs for the patients affected. CONCLUSIONS: Coagulase negative staphylococci are the most important pathogens in deep postoperative infections in this material. They cause infections that are difficult to recognize since they give only discrete symptoms and start well after the patients leave the hospital. The risk factors for patients with CoNS infections are mostly associated with a long exposure to the hospital environment. The treatment is often difficult and costly because of multiresistant bacteria and frequent need for repeated surgical revisions.