Pertrochanteric hip fracture is associated with mobility decline and poorer physical performance 4 to 6 months post-hip fracture.

BACKGROUND: To study the effect of hip fracture type on physical performance, functional ability and change in mobility four to six months after the injury. METHODS: A total of 1331 patients out of consecutive 2052 patients aged ≥ 65 years who underwent hip fracture surgery were included in the study. Patient information was collected on admission, during hospitalization, by phone interview and at the geriatric outpatient clinic 4 to 6 months after the fracture. Of the 1331 eligible patients, Grip strength, Timed Up and Go -test (TUG), Elderly Mobility Scale (EMS), mobility change compared to pre-fracture mobility level, Basic Activities of Daily Living (BADL) and Instrumental Activities of Daily Living (IADL) were used to determine physical performance and functional ability. Logistic regression was used for the analyses which was adjusted for gender, age, American Society of Anesthesiologists score, diagnosis of cognitive disorder, pre-fracture living arrangements, mobility and need of mobility aid. RESULTS: Patients with pertrochanteric hip fracture had an EMS lower than 14 (Odds Ratio (OR) 1.38, 95% confidence intervals (CI) 1.00-1.90), TUG time ≥ 20 s (OR 1.69, 95% CI 1.22-2.33) and they had declined in mobility (OR 1.58, 95% CI 1.20-2.09) compared to femoral neck fracture patients 4 to 6 months post-hip fracture in multivariable-adjusted logistic regression analyses. Grip strength and functional ability (IADL, BADL) 4 to 6 months after hip fracture did not differ between fracture types. There were no statistically significant differences in physical performance in patients with a subtrochanteric fracture compared to patients with a femoral neck fracture. CONCLUSIONS: Pertrochanteric hip fracture independently associated with poorer physical performance 4 to 6 months post hip fracture compared to other hip fracture types. Pertrochanteric hip fracture patients should be given special attention in terms of regaining their previous level of mobility.

Urinary and double incontinence in older women with hip fracture - risk of death and predictors of incident symptoms among survivors in a 1-year prospective cohort study.

OBJECTIVES: To investigate the association of urinary incontinence (UI) and double incontinence (DI, concurrent UI and fecal incontinence) with one-year mortality among older female hip fracture patients and to identify predictors of incident UI and DI. DESIGN: A prospective cohort study SETTING AND SUBJECTS: 1,468 female patients aged ≥ 65 treated for their first hip fracture during the period 2007-2019 METHODS: Continence status was elicited at baseline and one-year post-fracture. Age- and multivariable-adjusted Cox proportional hazards and multinomial logistic regression models were used to determine the associations of incontinence with one-year mortality and to examine the associations of baseline predictors with incident UI and DI respectively. RESULTS: Of the women with no incontinence, UI and DI, 78 (13%), 159 (23%) and 60 (34%), died during follow-up. UI (HR 1.72, 95% CI 1.31-2.26) and DI (HR 2.61, 95% CI 1.86-3.66) were associated with mortality after adjusting for age. These associations lost their predictive power in multivariable analysis while age over 90, living in an institution, impaired mobility, poor nutrition, polypharmacy, and late removal of urinary catheter remained associated with mortality. Of continent women, 128 (21%) developed UI and 23 (4%) DI during follow-up. In multivariable analysis, impaired mobility was associated with incident UI (OR 2.56, 95% CI 1.48-4.44) and DI (OR 4.82, 95% CI 1.70-13.7), as well as living in an institution (OR 3.44, 95% CI 1.56-7.61 and OR 3.90, 95% CI 1.17-13.0). CONCLUSIONS AND IMPLICATIONS: Underlying vulnerability likely explains differences in mortality between continence groups and development of incident UI and DI.

Factors associated with and 1-year outcomes of fear of falling in a geriatric post-hip fracture assessment.

BACKGROUND: Hip fracture causes not only physical injury but also psychological trauma. Fear of falling (FoF) is related to poor recovery, loss of mobility and mortality. There is limited data on the clinical factors affecting post-hip fracture FoF and its consequences. OBJECTIVE: To investigate the factors associated with and 1-year outcomes of post-hip fracture FoF. METHODS: An observational prospective cohort study. Data were collected on hospital admission, at a geriatric outpatient assessment 4-6 months post-hip fracture and by telephone interviews 1 year after the index fracture. FoF was assessed with a dichotomous single-item question. Logistic regression analyses were conducted to examine the age, gender and multivariable-adjusted association between baseline and the geriatric assessment domains with FoF. Follow-up outcomes included changes in mobility, living arrangements and mortality. RESULTS: Of the 916 patients included, 425 (49%) had FoF at the time of their geriatric assessment. These patients were predominantly female and were living alone in their own homes with supportive home care. They scored lower on tests of physical performance. Less FoF was documented in patients with diagnosed cognitive disorders before the index fracture and in those with Clinical Dementia Rating ≥ 1. After adjusting for age and gender, no association was observed between FoF and any of the 1-year follow-up outcomes. CONCLUSION: Post-hip fracture FoF is common and associated with female gender, polypharmacy, poor daily functioning, poor physical performance and depressive mood. Patients with cognitive disorders have less FoF than those without. FoF appears to have no impact on the follow-up outcomes.

Prevalence of autoimmune disorders among bladder pain syndrome patients' relatives.

PURPOSE: Possible genetic background and autoimmune etiology of Bladder Pain Syndrome (BPS, formerly Interstitial Cystitis, IC) has been suggested. We studied whether familial clustering of BPS, other autoimmune diseases or fibromyalgia exist among BPS patients' genetically close relatives; possibly reflecting some common predisposing genetic background of these diseases. MATERIALS AND METHODS: Altogether 420 first- or second-degree relatives of 94 BPS patients fulfilling the NIDDK criteria were asked to fill in a survey on the self-reported diagnosis of urinary tract diseases, fibromyalgia and 23 autoimmune diseases, together with filling the O'Leary-Sant symptom score. The ones with high symptom scores were interviewed and, if necessary, referred to a further clinical consultation. The prevalence of other diseases was compared to previously published prevalence percentages. RESULTS: 334 (80%) of 420 family members returned the questionnaire. Only one of the relatives fulfilled the NIDDK criteria, and one sibling pair among the original BPS patients was found. Asthma, ulcerative colitis, fibromyalgia, iritis and rheumatoid arthritis were more common in the study population than in the reference populations. The reported prevalence of atopic dermatitis and rhinoconjunctivitis causing allergies were lower. In addition, the results show that the O'Leary-Sant symptom score is not reliable in screening for new BPS cases. CONCLUSIONS: Our study suggests that in BPS patients' families, fibromyalgia and autoimmune diseases including asthma, and especially the non-allergic form of asthma, may be over-represented.

Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome predisposing to cutaneous and uterine leiomyomatosis as well as renal cell cancer and uterine leiomyosarcoma. Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene are known to cause HLRCC. On occasion, no FH mutation is detected by direct sequencing, despite the evident HLRCC phenotype in a family. In the present study, to investigate whole gene or exonic deletions and amplifications in FH mutation-negative patients, we used multiplex ligation-dependent probe amplification technology. The study material comprised 7 FH mutation-negative HLRCC patients and 12 patients affected with HLRCC-associated phenotypes, including papillary RCC, early-onset RCC, uterine leiomyomas, or uterine leiomyosarcoma. A novel FH mutation, a deletion of FH exon 1 that encodes the mitochondrial signal peptide, was detected in one of the HLRCC patients (1/7). The patient with the FH mutation displayed numerous painful cutaneous leiomyomas and papillary type renal cell cancer. Our finding, together with the two patients with whole FH gene deletion who had been detected previously, suggests that exonic or whole-gene FH deletions are not a frequent cause of HLRCC syndrome.

Expression of ion transport-associated proteins in human efferent and epididymal ducts.

Appropriate intraluminal microenvironment in the epididymis is essential for maturation of sperm. To clarify whether the anion transporters SLC26A2, SLC26A6, SLC26A7, and SLC26A8 might participate in generating this proper intraluminal milieu, we studied the localization of these proteins in the human efferent and the epididymal ducts by immunohistochemistry. In addition, immunohistochemistry of several SLC26-interacting proteins was performed: the Na(+)/H(+) exchanger 3 (NHE3), the Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR), the proton pump V-ATPase, their regulator Na(+)/H(+) exchanger regulating factor 1 (NHERF-1), and carbonic anhydrase II (CAII). Our results show that SLC26A6, CFTR, NHE3, and NHERF-1 are co-expressed on the apical side of the nonciliated cells, and SLC26A2 appears in the cilia of the ciliated cells in the human efferent ducts. In the epididymal ducts, SLC26A6, CFTR, NHERF-1, CAII, and V-ATPase (B and E subunits) were co-localized to the apical mitochondria rich cells, while SLC26A7 was expressed in a subgroup of basal cells. SLC26A8 was not found in the structures studied. This is the first study describing the localization of SLC26A2, A6 and A7, and NHERF-1 in the efferent and the epididymal ducts. Immunolocalization of human CFTR, NHE3, CAII, and V-ATPase in these structures differs partly from previous reports from rodents. Our findings suggest roles for these proteins in male fertility, either independently or through interaction and reciprocal regulation with co-localized proteins shown to affect fertility, when disrupted.

SLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human kidney.

BACKGROUND: The anion transporters SLC26A6 (PAT1) and SLC26A7, transporting at least chloride, oxalate, sulfate and bicarbonate, show a distinct expression and function in different mammalian species. They are expressed in kidney, but their exact localization in human kidney has not been studied. We therefore examined SLC26A6 and A7 expression in human kidneys. METHODS: The localization of SLC26A6 and A7 in different segments of human nephrons was studied by RT-PCR and immunohistochemistry by comparing to the tubular markers PNRA, CD10, Tamm-Horsfall antigen, high molecular weight cytokeratin, CK7, AQP2 and H(+)V-ATPase. RESULTS: In human kidney, SLC26A6 is expressed in distal segments of proximal tubules, parts of the thin and thick ascending limbs of Henle's loops, macula densa, distal convoluted tubules and a subpopulation of intercalated cells of collecting ducts. SLC26A7 is expressed in extraglomerular mesangial cells and a subpopulation of intercalated cells of collecting ducts. CONCLUSION: Our results show that in human kidney SLC26A6 and A7 have a distinct, partially overlapping expression in distal segments of nephrons. The distribution partly differs from that found previously in rodent kidneys.

Isoforms of SLC26A6 mediate anion transport and have functional PDZ interaction domains.

The solute carrier gene family SLC26 consists of tissue-specific anion exchanger genes, three of them associated with distinct human recessive disorders. By a genome-driven approach, several new SLC26 family members have been identified, including a kidney- and pancreas-specific gene, SLC26A6. We report the functional characterization of SLC26A6 and two new alternatively spliced variants, named SLC26A6c and SLC26A6d. Immunofluorescence studies on transiently transfected cells indicated membrane localization and indicated that both NH(2)- and COOH-terminal tails of the SLC26A6 variants are located intracellularly, suggesting a topology with an even number of transmembrane domains. Functional expression of the three proteins in Xenopus oocytes demonstrated Cl(-) and SO(4)(2-) transport activity. In addition, the transport of SO(4)(2-) and Cl(-) was inhibited by DIDS and HCO(3)(-). We demonstrated also that the COOH terminus of SLC26A6 binds to the first and second PDZ domains of the Na(+)/H(+) exchanger (NHE)3 kinase A regulatory protein (E3KARP) and NHE3 regulatory factor (NHERF) proteins in vitro. Truncation of the last three amino acids (TRL) of SLC26A6 abrogated the interaction but did not affect transport function. These results demonstrate that SLC26A6 and its two splice variants can function as anion transporters linked to PDZ-interaction pathways. Our results support the general concept of microdomain organization for ion transport and suggest a mechanism for cystic fibrosis transmembrane regulator (CFTR)-mediated SLC26A6 upregulation in pancreatic duct cells.

Functional characterization of three novel tissue-specific anion exchangers SLC26A7, -A8, and -A9.

A second distinct family of anion exchangers, SLC26, in addition to the classical SLC4 (or anion exchanger) family, has recently been delineated. Particular interest in this gene family is stimulated by the fact that the SLC26A2, SLC26A3, and SLC26A4 genes have been recognized as the disease genes mutated in diastrophic dysplasia, congenital chloride diarrhea, and Pendred syndrome, respectively. We report the expansion of the SLC26 gene family by characterizing three novel tissue-specific members, named SLC26A7, SLC26A8, and SLC26A9, on chromosomes 8, 6, and 1, respectively. The SLC26A7-A9 proteins are structurally very similar at the amino acid level to the previous family members and show tissue-specific expression in kidney, testis, and lung, respectively. More detailed characterization by immunohistochemistry and/or in situ hybridization localized SLC26A7 to distal segments of nephrons, SLC26A8 to developing spermatocytes, and SLC26A9 to the lumenal side of the bronchiolar and alveolar epithelium of lung. Expression of SLC26A7-A9 proteins in Xenopus oocytes demonstrated chloride, sulfate, and oxalate transport activity, suggesting that they encode functional anion exchangers. The functional characterization of the novel tissue-specific members may provide new insights to anion transport physiology in different parts of body.