Association of Double-J Stenting in Renal Transplant Patients With Urinary Tract Colonization and Infections in a Multidrug-resistant Microbe Endemic Nosocomial Environment.

PURPOSE: We investigated the association of ureteral stenting after kidney transplantation with the development of urinary tract infections (UTIs) and/or urinary tract colonization, in a hospital environment considered endemic for multidrug resistant (MDR) Gram-negative Enterobacteriaceae. METHODS: Seventy-five recipients of deceased donor grafts were divided in groups A and B. Group A (with subgroups A1 and A2) included 45 transplanted patients without urinary stenting, and group B 30 patients with stenting. Subgroup A1 consisted of 30 patients transplanted before 2006, and A2 of 15 patients transplanted after 2006, when MDR, mainly carbapenem-resistant, Enterobacteriaceae, frequency has risen in our hospital. RESULTS: The incidence and the number of UTIs per patient were significantly higher in patients without stenting compared to those with stenting. (Group A: 32/45 vs group B: 9/30, P < .001, and group A: 2.86 ± 0.43 vs group B: 0.6 ± 0.19, P < .01 respectively). Patients without stenting tended to have a higher frequency of recurrent UTIs compared to those with stenting (group A: 16/45 vs group B: 4/30, P < .05). Asymptomatic bacteriuria was more frequent in the patients with stent (group A: 8/45 vs group B: 14/30, P < .05). Further sub-comparison of the A1 and A2 subgroups with group B did not change the statistical results. CONCLUSIONS: There is no clinically significant association of ureteral stenting after kidney transplantation with the high frequency of MDR Gram-negative bacteria in our hospital.

Fulminant Epstein-Barr virus-associated hemophagocytic syndrome in a renal transplant patient and review of the literature.

We describe a rare fulminant case of Epstein-Barr virus-associated hemophagocytic syndrome (HPS) in a 37-year-old female renal transplant patient, indistinguishable from severe sepsis clinically and in the laboratory. HPS involves rapidly escalating immune system activation, resulting in a cytokine cascade, which can, especially in immunocompromised patients, lead to multi-organ failure, and even death. Thirty-two Herpesviridae-associated HPS cases in renal transplant patients have been reported and are reviewed. Overall mortality is 47% (15/32 cases).

Epidemiology and outcome of elderly admitted to the ward for sepsis.

BACKGROUND: The elderly represent a significant cohort of patients presenting at the emergency department, especially in the developed countries. They are characterized by impaired physical condition, comorbidities, and little immune system resources and make frequent use of the healthcare system and its facilities. This study aimed to describe the features and prognostic factors of sepsis in elderly patients (>60 years old) admitted to an internal medicine ward. MATERIAL AND METHODS: Two hundred eighty eight consecutively patients aged >60 years who were admitted with sepsis during a two-year-period were retrospectively included in the study. Clinical and laboratory parameters at presentation were analyzed. Causes of sepsis and biochemical markers were compared between the healthcare facility-naïve and the healthcare facility-exposed groups. The effect of comorbidities and previous exposure to the healthcare system on clinical course and outcome of the patients was analyzed. RESULTS: Among the comorbidities that were recorded and included in the analysis, the presence of chronic and acute renal impairment and neurologic disabilities were associated with a worse outcome of sepsis in the elderly. In the same cohort, a previous contact with the healthcare system was found to affect the duration of hospital stay, but not the outcome per se. Sepsis-related markers, such as inflammatory markers were not found to be associated with clinical progression and outcome. CONCLUSIONS: Timely diagnosis and accurate evaluation of the severity of sepsis is required to ensure a better outcome for the patients. Sensitive markers and accurate prognostic models are constantly pursued. The impact of living characteristics of the modern aging society is additionally addressed and their effect on sepsis outcome assessed. Hippokratia 2016, 20(4): 274-278.

Acute inflammatory arthritis in the elderly; Old flames, new sparks.

BACKGROUND: The overall world prevalence of rheumatoid arthritis (RA) ranges from 0.5-1.0%. The annual incidence of RA in most European countries ranges from roughly 0.4 to >2.5 per 1,000 adults, increasing with age. A significant proportion of newly diagnosed cases will evolve into true erosive RA. METHODS: The aim of this cohort study was to study the characteristics of new developing, acute (<1 year), rheumatoid arthritis in an elderly (>65 years) population; its presenting features, accompanying manifestations and laboratory findings. One hundred twenty eight patients (103♀, 25♂) who presented to the rheumatology outpatients clinic with new-onset RA were included in the study. 42.2% of the patients had pre-existing osteoarthritis. RESULTS: At presentation, 14.3% of the patients had systemic manifestations (fever, weight loss), 25.78% reported concomitant sicca symptomatology, and 50.9% were found to have abnormal haematological parameters (anemia and/or thrombocytosis). Clinical and laboratory parameters of the disease were analyzed and related to disease manifestations.. Haematological abnormalities were found to be associated both with increased inflammatory markers, as well as with increased titres of rheumatoid factor (RF), but not anti - cyclic citrullinated peptide (CCP) antibodies, in contrary to systemic manifestations which were not found to be related to the above mentioned parameters. CONCLUSIONS: As the global population is becoming older, physicians will be challenged with the recognition and treatment of these conditions and their particular features in an increasing number of geriatric patients; within the context of the specific characteristics and comorbidities of this age group. Hippokratia 2014; 18 (3): 231-233.

The impact of frequently encountered cardiovascular risk factors on sexual dysfunction in rheumatic disorders.

Traditional cardiovascular risk factors have been acknowledged as major contributors to sexual dysfunction in the general population. The purpose of this study was to explore their impact on sexual function in rheumatologic patients. A total of 557 consecutive rheumatologic patients, 449 females and 108 males, had their sexual function evaluated with the Female Sexual Functioning Index (FSFI) and the International Index of Erectile Function (IIEF) questionnaire respectively. Personal data regarding presence of cardiovascular risk factors were collected and analysed in association with the FSFI and IIEF scores. Mean age of the participants was 54.1 ± 14.1 years, mean body mass index was 27.5 ± 5.29 and mean systolic and diastolic blood pressure was 130.5 ± 19.82 and 79.5 ± 10.51 mmHg respectively. Hypertension was present in 39% of the participants, diabetes mellitus in 10.2%, dyslipidaemia in 33.6% and history of cardiovascular events in 8.6%, whereas smoking was recorded by 28.4% and alcohol consumption by 7.4%. Sexual dysfunction affected 68.6% of our study population (73.5% of females and 48.1% of males, p < 0.001). Logistic regression analysis revealed that age was the only factor associated with a significantly higher prevalence of sexual dysfunction (p < 0.001 for both genders, p = 0.013 in males and p < 0.001 in females). Increased age was identified as the only independent predictor of sexual dysfunction in our population. Apart from age, traditional cardiovascular risk factors failed to explain the increased prevalence of sexual dysfunction in these patients. Other contributing factors (physical and/or psychological) might account for the increased occurrence of sexual dysfunction in rheumatic disorders.

Cerebral amyloid angiopathy.

The aim of this report was to describe the case of an elderly patient with cerebral amyloid angiopathy and associated dementia who presented with new onset symptomatology compatible with an acute cerebrovascular event. Computed tomography scanning was suggestive of an incipient ischemic cerebrovascular event. Magnetic resonance imaging was requested due to the presence of small hyperdense lesions on CT, and revealed multiple diffuse hypodense parenchymal lesions with hemosiderin deposits, indicative of cerebral amyloid angiopathy. Diagnosis of the underlying pathology is of importance, as aspirin use, and antiplatelet use in general, may in these patients be associated with microbleed burden.

Association of capillaroscopic microhaemorrhages with clinical and immunological antiphospholipid syndrome.

OBJECTIVES: Patients with clinical signs of vasculopathy were screened with capillaroscopy for microangiopathy, and its presence was evaluated in the diagnosis of antiphospholipid syndrome (APS). For this purpose, autoantibody profiles in high risk patients with microhaemorrhages were correlated with thrombotic events. METHODS: 738 patients from a Rheumatology Outpatients cohort were consecutively screened with capillaroscopy. Patients with microhaemorrhages were selected from the total of individuals screened and tested for anticardiolipin (αCL) and anti-beta2 glycoprotein 1 (anti-ß2GP1) Abs. Positive autoantibody profile was subsequently correlated with arterial and venous thrombotic events. Patients with scleroderma were excluded from the analysis. RESULTS: 149 patients with various rheumatologic conditions and capillary microhaemorrhages were included in the study. Antiphospholipid profile screening in these individuals revealed a 15.4% of newly diagnosed secondary laboratory APS. αCL antibodies and anti-ß2-glycoprotein 1 (anti-ß2GP1 Abs were both found to independently correlate significantly with thrombotic events. Subanalysis of the type of anti-ß2GP1 Abs indicated that the correlation with thrombotic events was significant for IgG-type (p<0.001) and IgM-type (p=0.051), but not IgA-type Abs (p=0.292). CONCLUSIONS: In patients with microhaemorrhages, αCL and anti-ß2GP1 Abs were associated with thrombotic events. The observation that, although IgA type-anti-ß2GP1 Abs were detected in patients with microangiopathy, they lacked any significant association with thrombotic complications, suggests, that either the type/conformation of the autoantibodies and/or additional factors may be critical for the development of thromboses. In conclusion, capillaroscopy can aid diagnostically to screen for or verify APS in combination with other parameters.

Inhibition of TNFalpha does not induce viral reactivation in patients with chronic hepatitis C infection: two cases.

Chronic infections, such as hepatitis C, in the setting of rheumatic disorders pose a potential hindrance to optimal management because of possible complications linked to the institution of immune suppression, as well as the high incidence of hepatotoxicity associated with many of the disease-modifying antirheumatic drugs included in the conventional therapeutic regimens. In the setting of hepatitis C, however, the effect of TNFalpha blockade may be potentially beneficial because TNFalpha appears to be involved in the pathogenesis of liver fibrosis through the stimulation of apoptotic pathways. Data related to this subject are, unfortunately, still limited and without detailed information regarding the clinical progression of the rheumatic disorder. We report the cases of two patients, one with ankylosing spondylitis and one with psoriatic arthritis, who were efficiently treated long-term with anti-TNF agents for their rheumatic disease without any evidence of reactivation or flaring of their hepatitis C infection or deterioration of their liver function. Our results indicate that TNFalpha blockade is a highly efficient and uncompromising therapy in hepatitis C-affected individuals with connective tissue disorders. However, systematic, large-scale studies addressing the issue of safety of these new efficient drugs, i.e., monoclonal antibodies targeted against TNFalpha, in patients with chronic hepatitis C will be needed to properly assess the risks and benefits of this treatment in analogous cases.

Prevalence of musculoskeletal disorders in patients with type 2 diabetes mellitus: a pilot study.

BACKGROUND: Diabetes mellitus is associated with a variety of musculoskeletal disorders. The prevalence of connective tissue disorders in these patients has increased in the recent years affecting significantly their quality of life. METHODS-RESULTS: We conducted a pilot study including 208 sequentially selected patients with type 2 diabetes mellitus regularly followed-up at the Diabetes Center of the Hippokration University Hospital. Among the diabetic patients who were screened according to the Short Musculoskeletal Function Assessment Questionnaire for musculoskeletal symptoms and findings, 82.6% were found to exhibit musculoskeletal abnormalities, mainly of the degenerative, noninflammatory type. CONCLUSIONS: Musculoskeletal disorders are a common finding among patients with type 2 diabetes. Obesity and accumulation of abnormally glycosylated byproducts have been proposed as potential pathogenetic mediators of these connective tissue abnormalities. Of particular interest is, however, the common association of osteoarthritis, involving even non-weight bearing joints in patients with type 2 diabetes, indicating a common pathophysiologic mechanism connecting these two clinical conditions.

Binding of heterochromatin protein 1 to the nuclear envelope is regulated by a soluble form of tubulin.

We have previously shown that the mouse heterochromatin protein 1 homologue M31 interacts dynamically with the nuclear envelope. Using quantitative in vitro assays, we now demonstrate that this interaction is potently inhibited by soluble factors present in mitotic and interphase cytosol. As indicated by depletion and order-of-addition experiments, the inhibitory activity co-isolates with a 55-kDa protein, which binds avidly to the nuclear envelope and presumably blocks M31-binding sites. Purification of this protein and microsequencing of tryptic peptides identify it as alpha2/6:beta2-tubulin. Consistent with this observation, bona fide tubulin, isolated from rat brain and maintained in a nonpolymerized state, abolishes binding of M31 to the nuclear envelope and aborts M31-mediated nuclear envelope reassembly in an in vitro system. These observations provide a new example of "moonlighting," a process whereby multimeric proteins switch function when their aggregation state or localization is altered.

Nuclear envelope breakdown in mammalian cells involves stepwise lamina disassembly and microtubule-drive deformation of the nuclear membrane.

We have studied nuclear envelope disassembly in mammalian cells by morphological methods. The first signs of nuclear lamina depolymerization become evident in early prophase as A-type lamins start dissociating from the nuclear lamina and diffuse into the nucleoplasm. While B-type lamins are still associated with the inner nuclear membrane, two symmetrical indentations develop on antidiametric sites of the nuclear envelope. These indentations accommodate the sister centrosomes and associated astral microtubules. At mid- to late prophase, elongating microtubules apparently push on the nuclear surface and eventually penetrate the nucleus. At this point the nuclear envelope becomes freely permeable to large ligands, as indicated by experiments with digitonin-treated cells and by the massive release of solubilized A-type lamins into the cytoplasm. At the prophase/prometaphase transition, the B-type lamina is fragmented, but 'islands' of lamin B polymer can still be discerned on the tips of congressing chromosomes. Finally, at metaphase, the lamin B polymer breaks down into small pieces, which tend to concentrate in the area of the mitotic spindle. Nuclear envelope breakdown is not prevented when the microtubules are depolymerized by nocodazole; however, the mode of nuclear lamina fragmentation in the absence of microtubules is markedly different from the normal one and involves multiple raffles and gaps, which develop rapidly along the entire surface of the nuclear envelope. These data suggest that nuclear envelope disassembly is a stepwise process in which the microtubules play an important part.

The inner nuclear membrane protein LAP1 forms a native complex with B-type lamins and partitions with spindle-associated mitotic vesicles.

We have examined the in situ organization and nearest neighbours of the 'lamina-associated polypeptide-1' (LAP1), a type II membrane protein and a major constituent of the mammalian nuclear envelope. We show here that, during interphase, LAP1 forms multimeric assemblies which are suspended in the inner nuclear membrane and are specifically associated with B-type lamins. The LAP1-lamin B complex is distinct from analogous complexes formed by the 'lamina-associated polypeptide-2' (LAP2), another inner nuclear membrane protein, and includes a protein kinase. Upon nuclear envelope breakdown, LAP1 partitions with mitotic vesicles which carry nuclear lamin B. The LAP1 vesicles can be distinguished from fragments of the nuclear envelope containing LAP2 and exhibit a striking co-alignment with spindle microtubules. These observations suggest that the inner nuclear membrane comprises discrete territories which accommodate specific integral membrane proteins and are differentially disassembled during mitosis.

The lamin B receptor (LBR) provides essential chromatin docking sites at the nuclear envelope.

Morphological studies have established that peripheral heterochromatin is closely associated with the nuclear envelope. The tight coupling of the two structures has been attributed to nuclear lamins and lamin-associated proteins; however, it remains to be determined which of these elements are essential and which play an auxiliary role in nuclear envelope-chromatin interactions. To address this question, we have used as a model system in vitro reconstituted vesicles assembled from octyl glucoside-solubilized nuclear envelopes. Comparing the chromosome binding properties of normal, immunodepleted and chemically extracted vesicles, we have arrived at the conclusion that the principal chromatin anchorage site at the nuclear envelope is the lamin B receptor (LBR), a ubiquitous integral protein of the inner nuclear membrane. Consistent with this interpretation, purified LBR binds directly to chromatin fragments and decorates the surface of chromosomes in a distinctive banding pattern.

Vimentin-associated mitotic vesicles interact with chromosomes in a lamin B- and phosphorylation-dependent manner.

We have assessed the involvement of the nuclear lamins in nuclear envelope reassembly. Analysis of perforated mitotic cells shows that A-type lamins are partly cytosolic and partly chromosome-bound, whereas B-type lamins are associated with vesicular structures throughout cell division. Lamin B-containing vesicles appear to dock on vimentin intermediate filaments during prometaphase, but dissociate from the cytoskeleton and assemble around chromatin at later phases of mitosis. Mitotic vesicles isolated from prometaphase cells en bloc with vimentin filaments can specifically capture chromosomes. Efficient chromosome capturing requires cytosolic factors and a dephosphorylating environment. Urea-stripping of the vesicles abolishes binding to chromosomes. However, reconstitution of the stripped membranes with purified B-type lamins restores their ability to bind to chromosomes in a cytosol- and dephosphorylation-dependent fashion. Vesicles reconstituted with B-type lamins form membraneous 'crescents' on the surfaces of chromosomes, but, unlike native vesicles, do not fuse into large sheets. From these observations we conclude that the initial targeting of mitotic vesicles to chromosomes is dependent on B-type lamins and on factors present in the mitotic cytoplasm. Apparently, further recruitment of membranes and fusion of chromosome-bound vesicles onto chromatin involves non-lamin peripheral membrane proteins.