Multimorbidity and functional impairment–bidirectional interplay,synergistic effects and common pathways

This review discusses the interplay between multimorbidity (i.e. co‐occurrence of more than one chronic health condition in an individual) and functional impairment (i.e. limitations in mobility, strength or cognition that may eventually hamper a person's ability to perform everyday tasks). On the one hand, diseases belonging to common patterns of multimorbidity may interact, curtailing compensatory mechanisms and resulting in physical and cognitive decline. On the other hand, physical and cognitive impairment impact the severity and burden of multimorbidity, contributing to the establishment of a vicious circle. The circle may be further exacerbated by people's reduced ability to cope with treatment and care burden and physicians’ fragmented view of health problems, which cause suboptimal use of health services and reduced quality of life and survival. Thus, the synergistic effects of medical diagnoses and functional status in adults, particularly older adults, emerge as central to assessing their health and care needs. Furthermore, common pathways seem to underlie multimorbidity, functional impairment and their interplay. For example, older age, obesity, involuntary weight loss and sedentarism can accelerate damage accumulation in organs and physiological systems by fostering inflammatory status. Inappropriate use or overuse of specific medications and drug–drug and drug–disease interactions also contribute to the bidirectional association between multimorbidity and functional impairment. Additionally, psychosocial factors such as low socioeconomic status and the direct or indirect effects of negative life events, weak social networks and an external locus of control may underlie the complex interactions between multimorbidity, functional decline and negative outcomes. Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age‐related health deterioration; this review provides an overview of knowledge gaps and future directions.     

Free insulin-like growth factor-I and cognitive function in older persons living in community.

CONTEXT: Increasing evidences from experimental and human studies suggest that the activity of the growth hormone (GH/insulin-like growth factor-I) axis may contribute to the age-related cognitive decline and poor cognition in late life. OBJECTIVE: The aim of the present study was to evaluate the relationship of total serum free IGF-I and its binding protein-3 with cognitive performance in older persons aged 80 years or older. DESIGN: Data are from baseline evaluation of the ilSIRENTE study (n=353). Cognitive performance was evaluated using five items enclosed in the Minimum Data Set for Home Care assessment form: short-term memory, procedural memory, cognitive skills in daily decision making, verbal expression, comprehension. Free insulin-like growth factor-I (free IGF-I) and IGF-binding protein-3 (IGFBP-3) in blood were measured. Analysis of covariance (ANCOVA) was used to examine the relationship between cognitive impairment and the serum free IGF-I and IGFBP-3 concentrations, after adjustment for potential confounding variables. RESULTS: After adjustment for potential confounders, which included age, gender, education, cerebrovascular disease, ischemic heart disease, congestive heart failure, hypertension, diabetes, depression, Parkinson diseases, thyroid diseases, smoking status, alcohol abuse, body mass index, and number of medications, individuals with verbal expression problems (n=20) and individuals with comprehension problems (n=24) had a significantly lower serum levels of readily dissociable IGF-I than participants without cognitive impairments. The serum IGFBP-3 presented the same behavior of free IGF-I. CONCLUSION: The present study suggests that among old-old subjects living in the community lower levels of total serum free IGF-I and IGFBP-3 are associated with impairment of cognitive performance. This finding suggests that the GH/IGF-I axis may play an important role in the age-related decline of cognitive performance.     

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.     

Functional decline in frail community-dwelling stroke patients

Patients who suffer a stroke event are at high risk of functional decline after the post-acute rehabilitation period. The aim of the present study was the evaluation of factors associated with functional decline in a large sample of older patients with stroke living in the community. The study population consisted of all patients admitted to home care programs after a post-acute rehabilitation program--with at least 1 year of follow-up--in twenty-two Italian Home Health Agencies from 2000 to 2002 (n=1338). For the present study we selected 355 (26%) patients with diagnosis of stroke. After 1 year of in-home care program, 149 out of 355 stroke survivors (42%) had presented a worsening in the activities of daily living (ADL) scale score. In the final adjusted model, patients with cognitive impairment (OR 2.59, 95% CI, 1.45-4.64), pressure ulcer (OR 2.74, 95% CI, 1.45-5.18), urinary incontinence (OR 1.64, 95% CI, 1.01-3.29), or hearing impairment (OR 1.83, 95% CI, 1.02-3.29) were more likely to significantly decline in physical functioning after a period of 1 year in-home care program. Our study documents that functional decline of stroke patients was largely dependent on specific subjects' clinical characteristics. Three of four concomitant disabling conditions associated in our sample with functional decline--pressure ulcer, urinary incontinence, hearing--can be prevented and eventually treated or modified. Appropriate post-acute rehabilitation programs and adequate home care interventions focused on the prevention and treatment of these conditions might be correlated to better outcomes in older post-stroke patients.     

Effects of gamma-hydroxybutyrate on cerebrospinal fluid lactate and glucose levels after spinal cord trauma.

This study aims to evaluate the effects of gamma-hydroxybutyrate (GHB) after spinal cord trauma (SCT). Twenty rabbits were divided equally into four groups: group I was the sham-operated group, group II suffered from SCT but received no treatment, group III was given a dose of 400 mg/kg of GHB intravenously before SCT and group IV received the same dose after SCT. Cerebrospinal fluid (CSF) samples were obtained 30 min before SCT (T(0)), at 60 (T(1)) and 120 min (T(2)) after SCT. There was a threefold increase in lactate levels from baseline value at T(2) in group II, while statistically significant elevation of the lactate levels were not observed in groups III and IV. Glucose levels at T(1) and T(2) were significantly lower in groups III and IV compared with the control group. The findings of this study demonstrate that GHB can control the increase of CSF lactate and glucose levels following SCT and that this metabolic effect may be associated with neuroprotective physiological changes.     

Is there any relationship between human leucocyte antigen class II and chronic urticaria? (chronic urticaria and HLA class II)

The Human Leukocyte Antigen (HLA) typing of large groups of patients with various autoimmune diseases has demonstrated that some HLA alleles occur at higher frequencies in specific diseases than in the general population. Chronic urticaria has been shown to have an autoimmune basis by a previous study which found an association between chronic urticaria and specific HLA groups. We investigated the HLA subtypes of Turkish chronic urticaria patients. For this purpose 42 Turkish patients with chronic urticaria and 115 healthy controls were typed for HLA-DR and DQ by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers) low resolution DNA technique. We found an increased frequency of DR4 (42.9%, p=0.01) in chronic urticaria patients in comparison with that in healthy controls. This study supports the hypothesis that HLA alleles may be involved in the pathogenesis of chronic urticaria and that they appear to be directly involved in the initiation of the immune response.     

Neuronal nuclear antigen (NeuN): a new tool in the diagnosis of central neurocytoma

The use of neuronal nuclear antigen (NeuN) as a reliable neuronal marker in the differential diagnosis of clear cell neoplasms of the central nervous system was determined in a biopsy series of 23 cases. Immunohistochemical analyses were carried out by antisera against neuronal nuclear antigen, synaptophysin, neuron-specific enolase, microtubule-associated protein 2, and glial fibrillary acidic protein. All eight central neurocytomas were characteristically immunolabeled by NeuN. NeuN immunoreactivity was uniformly strong and basically located in the nuclei of neurocytes. Despite this uniform staining pattern of central neurocytomas, 12 cases of oligodendrogliomas and three cases of ependymoma were negative for NeuN. As the diagnostic criteria for central neurocytoma include immunohistochemical and/or ultrastructural evidence for neuronal differentiation, NeuN as a sensitive and specific neuronal marker in formalin-fixed, paraffin-embedded tissues may greatly facilitate the differential diagnosis of central neurocytomas.     

Widal test in diagnosis of typhoid fever in Turkey

We studied the value of the Widal tube agglutination test for the diagnosis of typhoid fever. The subjects were all adults >18 years of age and were divided into four groups: (i) 317 healthy blood donor controls, (ii) 31 bacteriologically confirmed patients with Salmonella enterica serotype Typhi, (iii) 21 patients with a clinical diagnosis of typhoid fever, and (iv) 41 febrile nontyphoid patients. Blood donor controls were screened with a slide agglutination test for the Salmonella enterica serotype Typhi O and H antigens, and positives were then tested with the Widal test. Acute- and convalescent-phase sera from patients in groups 2, 3, and 4 were obtained 7 to 10 days apart and tested by the Widal test. Using a cutoff of >or = 1/200 for the O antigen test performed on acute-phase serum gave a sensitivity of 52% and a specificity of 88% with a positive predictive value (PPV) of 76% and a negative predictive value (NPV) of 71%. This increased to 90% sensitivity and specificity with a PPV of 88% and an NPV of 93% when the convalescent-phase serum was tested. We concluded that O and H agglutinin titers of > or = 1/200 are of diagnostic significance. The Widal test is easy, inexpensive, and relatively noninvasive. It can be of diagnostic value when blood cultures are not available or practical. The results must be interpreted cautiously because of the low sensitivity of the test. The Widal test done on convalescent-phase serum gave more-reliable results with higher specificity and sensitivity.     

Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche

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Effectiveness of the caverno-dorsal vein shunt (Barry shunt) on prolonged ischaemic priapism and its effect on the post-operative long-term erectile function

Ischaemic priapism is the most common form of priapism and requires urgent treatment. In this study, we evaluated the effectiveness of the caverno-dorsal vein shunt on resolution of ischaemic priapism and on the post-operative long-term erectile function in patients presenting with priapism. The study included 10 patients admitted to our hospital for priapism between 2010 and 2018. The median age of the patients was 31 (24–66) years. The median priapism time was 13.5 (7–38) hours. The blood gas measurements were taken from the corpus cavernosum, and the drainage of the corpus cavernosum was performed as an emergency intervention. Then, the corpus cavernosum was irrigated with 0.01% adrenaline 5 times in 20-min intervals. The caverno-dorsal vein shunt procedure was performed in cases without regression of priapism. Two months after, the operation shunt was closed. Detumescence occurred in all patients. Eight of 10 patients maintained their erectile function. In 2 patients, severe erectile dysfunction occurred at post-operative 2 months following a priapism attack and penile prosthesis implantation was performed in these 2 patients. Our study showed that caverno-dorsal vein shunt procedure is effective in providing detumescence and maintaining potency in cases with ischaemic priapism. In our opinion, caverno-dorsal vein shunt can be considered as the first treatment of choice for refractory low-flow priapism.