Patterns of gastrointestinal injury in patients with chronic kidney disease: Comparison of cases with and without sevelamer crystals.

AIMS: Sevelamer is a phosphate-binding resin implicated in gastrointestinal (GI) injury. This study aimed to investigate the role of sevelamer in GI injury among chronic kidney disease (CKD) patients. METHODS AND RESULTS: The study included 17 CKD patients (cases) with and 18 CKD patients (comparisons) without sevelamer crystals in specimens. All cases were on sevelamer. Six comparison patients were also taking sevelamer, but crystals were absent in tissue sections. The comparison group was thus subclassified into patients who were and were not taking sevelamer. The frequency of underlying disorders was similar between two groups, including hypertension (cases = 82%; comparisons = 78%) and diabetes mellitus (cases = 53%, comparisons = 50%). The most common presentation was GI bleeding (cases = 41%, comparisons = 33%). Predominant histological patterns were also similar, with ulcers (cases = 42%; comparisons = 39%) and acute ischaemia (cases = 35%; comparisons = 28%) being predominant in both cohorts. Of note, sevelamer was present with amyloidosis and cytomegalovirus in one study case each. Two study patients who continued sevelamer had follow-up biopsies; one showed persistent ulceration and the other appeared normal. Crystals were absent in both. CONCLUSIONS: GI injury in CKD patients in both groups had similar features regardless of presence of sevelamer, suggesting that it adheres to tissue rather than causes injury. The study highlights other histologically identifiable causes of intestinal injury, as well as injuries unassociated with sevelamer in patients undergoing therapy. Therefore, physicians should be cautious in attributing GI injuries to sevelamer to avoid overlooking other causes and unnecessary treatment discontinuation.

ALDH1 expression predicts progression of premalignant lesions to cancer in Type I endometrial carcinomas.

In type 1 endometrial cancer, unopposed estrogen stimulation is thought to lead to endometrial hyperplasia which precedes malignant progression. Recent data from our group and others suggest that ALDH activity mediates stemness in endometrial cancer, but while aldehyde dehydrogenase 1 (ALDH1) has been suggested as a putative cancer stem cell marker in several cancer types, its clinical and prognostic value in endometrial cancer remains debated. The aim of this study was to investigate the clinical value of ALDH1 expression in endometrial hyperplasia and to determine its ability to predict progression to endometrial cancer. Interrogation of the TCGA database revealed upregulation of several isoforms in endometrial cancer, of which the ALDH1 isoforms collectively constituted the largest group. To translate its expression, a tissue microarray was previously constructed which contained a wide sampling of benign and malignant endometrial samples. The array contained a metachronous cohort of samples from individuals who either developed or did not develop endometrial cancer. Immunohistochemical staining was used to determine the intensity and frequency of ALDH1 expression. While benign proliferative and secretory endometrium showed very low levels of ALDH1, slightly higher expression was observed within the stratum basalis. In disease progression, cytoplasmic ALDH1 expression showed a step-wise increase between endometrial hyperplasia, atypical hyperplasia, and endometrial cancer. ALDH1 was also shown to be an early predictor of EC development, suggesting that it can serve as an independent prognostic indicator of patients with endometrial hyperplasia with or without atypia who would progress to cancer (p = 0.012).

Aldehyde dehydrogenase isoforms and inflammatory cell populations are differentially expressed in term human placentas affected by intrauterine growth restriction.

OBJECTIVE: Intrauterine growth restriction (IUGR) is a complication of pregnancy that has both short- and long-term sequelae for affected mothers and offspring. The pathophysiology of disease stems from poor nutrient and oxygen provision to the fetus, resulting in increased oxidative stress within the placenta. As the milieu within the local microenvironment alters macrophage differentiation, we hypothesized that macrophage plasticity may be altered in placentas associated with IUGR, and that macrophages would show hallmarks of lipid peroxidation including altered aldehyde metabolism. METHODS: In human placentas taken from normal pregnancies resulting in appropriate-for-gestational-age (AGA) newborns and placentas associated with IUGR, placental macrophages were evaluated by immunohistochemistry and shown in IUGR to resemble pro-inflammatory activated M1-type macrophages. To link oxidative stress to macrophages, the expression of aldehyde dehydrogenase (ALDHs) isozymes ALDH1, ALDH2, and ALDH3 was assessed. RESULTS: All three isozymes displayed preferential staining for distinct cellular populations within the term human placenta. ALDH1 and ALDH2 were strongly expressed in placental Hofbauer and decidual stromal cells. ALDH3, in contrast, was present in extravillous trophoblasts. Comparing AGA and IUGR-associated placentas, ALDH1 and ALDH2 trended to have greater expression in macrophage populations but lower expression in decidual cell populations in IUGR-associated placentas. ALDH3 had higher expression in IUGR-associated placentas but localized specifically to extravillous trophoblast populations. CONCLUSION: Therefore, we speculate that specific ALDH isozymes have cell-specific functions related to differentiation, inflammation, or oxidative stress responses that are altered in IUGR-associated term human placentas. This family of isozymes may be a novel method to identify human placentas affected by placental insufficiency/IUGR.

Antineutrophil cytoplasmic antibody-associated vasculitis, update on molecular pathogenesis, diagnosis, and treatment.

Circulating antineutrophil cytoplasmic antibodies (ANCAs) are the central pathogenic mechanism for a group of systemic and renal syndromes called the ANCA-associated vasculitis (AAV). The nomenclature has changed from eponymous labeling to granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and microscopic polyangiitis. These syndromes predominantly affect the pulmonary and renal systems. We also review the molecular pathology behind ANCAs and associated antigens and infections. Various clinical presentations, the multiple target organs affected, and diagnostic challenges involved in identifying these diseases are discussed. Treatment updates are also provided with regard to new studies and the now standard use of anti-CD-20 monoclonal antibodies as first-line therapy in all but the most aggressive presentations of this disease. Maintenance regimens and monitoring strategies for relapse of vasculitis and associated systemic complications are discussed.

Erdheim-Chester Disease Presenting with Secondary Hypertension as a Result of Bilateral, Proximal Renal Artery Stenosis: A Case Report.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis presenting most commonly with bone and central nervous system symptoms, including but not limited to bone pain and diabetes insipidus. We present a known case of ECD, which was referred for secondary hypertension workup and diagnosed with severe, proximal, bilateral renal artery stenosis.

A Case of Kidney Involvement in Primary Sjögren's Syndrome.

BACKGROUND Sjögren's syndrome is an autoimmune disorder caused by the infiltration of monocytes in epithelial glandular and extra-glandular tissues. Hallmark presentations include mouth and eye dryness. Although renal involvement is uncommon in primary Sjögren's syndrome (pSS), patients may experience renal tubular acidosis type I (RTA I), tubulointerstitial nephritis, diabetes insipidus (DI), nephrolithiasis, and Fanconi syndrome. However, it is atypical to see more than 1 of these manifestations in a single patient. CASE REPORT We present the case of a 24-year-old woman with polyuria and polydipsia, who was initially diagnosed with nephrogenic diabetes insipidus. She also had chronic hypokalemia and nephrolithiasis. Based on clinical presentation and work up, she was diagnosed with pSS and treated accordingly. CONCLUSIONS This was a pSS patient with tubulointerstitial nephritis, diabetes insipidus, renal tubular acidosis, hypokalemia, and nephrolithiasis, who was receiving symptomatic treatment for diabetes insipidus. Diagnosis and treatment of pSS led to significant improvement in systemic and renal presentations of the patient. pSS should be considered as one of the differential diagnoses in patients with diabetes insipidus and renal tubular acidosis.

Eccrine Nevus Presenting with Umbilical Discharge: A Case Report and Review of the Literature.

Eccrine nevus is a rare skin lesion with protean manifestations like hyperhidrosis, discolored nodules, papules, and so forth, which has been reported in various anatomic parts of the body including the forearm, leg, thigh, back, and coccyx. Our patient was a 26-year-old male, who presented with increasing colorless and odorless episodic umbilical discharge. First impression for the patient was an umbilical sinus and the patient underwent surgery. Histopathological study revealed the lesion to be an eccrine nevus of the umbilicus. This is the first case of eccrine nevus presenting with umbilical discharge. We recommend that eccrine nevus should be considered as a differential diagnosis for umbilical discharge.

C-reactive protein as an available biomarker determining mental component of health-related quality of life among individuals with spinal cord injury.

OBJECTIVES: C-reactive protein (CRP) has been shown to correlate with health-related quality of life (HRQL) in some chronic medical conditions. However, these associations have not yet described in spinal cord injury (SCI). In this study, we tried to identify biomarkers associated with HRQL in SCI. DESIGN: Cross-sectional. SETTING: Tertiary rehabilitation center. PARTICIPANTS: Referred patients to Brain and Spinal Cord Injury Research Center between November 2010 and April 2013. OUTCOME MEASURE: Blood samples were taken to measure circulatory CRP, leptin, adiponectin, ferritin, parathyroid hormone, calcitonin, thyroid hormones, fasting plasma glucose and lipid profile. All the analyses were performed with adjustment for injury-related confounders (level of injury, injury completeness and time since injury) and demographic characteristics. HRQL was measured with Short Form health survey (SF-36). RESULTS: The initial inverse association between CRP and total score of SF-36 (P: 0.006, r = -0.28) was lost after adjustment for confounders. However, the negative correlation between CRP and Mental Component Summary (MCS) remained significant (P: 0.0005, r = -0.38). Leptin level was inversely correlated with Physical Component Summary (PCS) (P: 0.02, r = -0.30). CONCLUSION: Although CRP and leptin levels were not related with total scores of SF-36 questionnaire, CRP can be more useful in determining mental component of HRQL whereas leptin can be a determinant of physical component. The combined consideration of these two biomarkers may help to predict HRQL in individuals with SCI.

The Influence of Pain, Weakness and Rheumatoid Factor Status on Depression Incidence Among Iranian Patients With Rheumatoid Arthritis.

BACKGROUND: Increased prevalence of depression among patients with Rheumatoid arthritis (RA) has been described previously. However, the impact of depression among Iranian patients has not yet been investigated. OBJECTIVES: Here, the prevalence of depression was assessed and the effect of disease-related characteristics including pain, weakness and rheumatoid factor (RF) status on incidence of depression was evaluated. MATERIALS AND METHODS: Patients with RA, who were referred to rheumatology clinics of Kermanshah University of Medical Sciences and healthy subjects from the general population of Kermanshah participated in this investigation. Depression was assessed using Beck's depression inventory II (BDI II). Pain and weakness were assessed subjectively by patients' self-report. Data was collected during a year between 2012 and 2013. Chi-square test and independent t-test were used. RESULTS: One hundred and seventy-one patients with RA and 198 healthy individuals participated in this investigation. In the RA group, depressive mood was detected in 45.7% of patients, which was significantly higher than healthy subjects (P = 0.008). Depression was more common in elderly patients (> 50 years old) in comparison with healthy subjects at a similar age (P = 0.03). Pain and weakness had no influence on depression incidence (P = 0.14 and 0.19, respectively) whereas patients with negative RF status were significantly more susceptible to severe depression (P: 0.001). CONCLUSIONS: Depression is more common among Iranian patients with RA (45%) than healthy subjects regardless of gender. Depression has a significant association with older age. Negative RF status may predict future risk of depression.

The Relationship Between Dietary Intakes of Amino Acids and Bone Mineral Density Among Individuals with Spinal Cord Injury.

OBJECTIVES: The effect of dietary protein intake on bone mineral density (BMD) has not been explained in patients with spinal cord injury (SCI). In this study, we looked at the relationship between BMD and higher protein intake in patients with SCI while controlling for possible confounders. METHODS: Patients with SCI, who were referred to the Brain and Spinal Cord Injury Research Center between November 2010 and April 2012, were included in the study. In total, the dietary intakes of 103 patients were assessed by 24-hour dietary recall interviews. We used dual-energy X-ray absorptiometry to measure BMD in the femoral neck, trochanter, intertrochanteric zone, hip, and lumbar vertebras. RESULTS: Eighty-six men and 17 women participated in this study. Protein intake was negatively associated with the BMD of lumbar vertebrae (p = 0.001, r = -0.37 for T-score and p = 0.030, r = -0.24 for Z-score). The BMD of lumbar vertebrae were negatively associated with intake of tryptophan, isoleucine, lysine, cysteine, and tyrosine (p = 0.007, 0.005, 0.009, 0.008, and 0.008 for T-score, respectively). Higher intakes of threonine, leucine, methionine, phenylalanine, valine, and histidine were related to a lower BMD of lumbar vertebrae (p = 0.006, 0.010, 0.009, 0.010, 0.009, and 0.008 respectively for T-scores). CONCLUSIONS: We found that high protein intake led to a lower BMD of lumbar vertebrae in patients with SCI after controlling for confounders including demographic and injury-related characteristics and calcium intake. No relationship between higher amino acids intake and BMD of the femur and hip was detected. Intake of alanine, arginine, and aspartic acid were not related to BMD.

Demographic study of pituitary adenomas undergone trans-sphenoidal surgery in Loghman Hakim Hospital, Tehran, Iran 2001-2013.

BACKGROUND: Pituitary adenomas (PAs) are abnormal benign tumors that develop in the pituitary gland. This study aimed to assess the prevalence of different types of PAs with an indication for trans-sphenoidal surgery in a well-defined population referred to Loghman Hakim Hospital during 2001-2013. SUBJECTS AND METHODS: In this retrospective study, the prevalence rate and symptoms associated with pituitary mass and hormone excess in operated patients were investigated. The diagnosis was verified after retrieval of clinical, hormonal, radiological, and pathological data. Demographic data were collected in all cases. Descriptive analysis, t-test, one-way analysis of variance and Fischer exacts test were used. RESULTS: A total of 278 patients with PAs who underwent surgical interventions were evaluated. Most of the patients were aged 40-50 years with an average of 41 ± 14. The most prominent complaint was pressure effect, which was detected in 153 cases (55.2%). At the second place, hormonal disorders were observed in 125 cases (44.8%). Type of pituitary tumors were: Prolactinomas (29.1%), growth hormone (GH)-producing tumors (25%), nonfunctioning PAs (28.4%), adrenocorticotropic hormone (ACTH)-producing tumors (2.1%), thyroid stimulating hormone (TSH)-producing tumors (0.7%), GH/prolactin (13.6%), GH/ACTH (0.3%), and TSH/ACTH (0.3%). Fifty-seven patients presented with recurrent adenomas. Pituitary apoplexy was found in 11 patients. One case of Sheehan syndrome was recorded among these. The correlations between clinical symptoms and patients, age and sex were not significant. CONCLUSION: The overview of demographic characteristics in Iranian patients with PAs with surgical indication has been discussed in the present investigation. The prevalence of different types of PAs and the most common clinical symptoms have been demonstrated.

Association of Coping Styles with Quality of Life in Cancer Patients.

BACKGROUNDS AND AIM: Cancer patients experience a high level of stress caused by the disease and treatment processes. Dealing with cancer using more beneficial coping styles can effectively improve the quality of life (QOL) and reduce the side effects of cancer, and it is treatment. In this study, we aimed to investigate the relationship between coping styles and QOL in cancer patients. METHODS: The study was performed on 150 cancer patients (71 females and 79 males) admitted to the hospitals affiliated with Kermanshah University of Medical Sciences. Endler and Parker Coping Inventory for Stressful Situations, and World Health Organization's Quality of Life Questionnaire were used to evaluate their coping style and QOL, respectively. RESULTS: The Present study showed in cancer patients being male, single, having higher salary and education, and lower age are related to higher QOL. Furthermore, in general, QOL of cancer patients was positively correlated with avoidant coping style (P < 0.05, r : 0.170) and negatively associated with emotion-focused coping styles (P < 0.01, r : -0.378). CONCLUSION: The results suggested that focusing on a patient's coping style, predominantly on an emotion-focused coping style, is essential to improve patient's QOL, and that patients possibly to employ a more emotion-oriented coping style should receive enough notice, particularly before discharge.

The Effect of Injury-Related Characteristics on Changes in Marital Status after Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) imposes a significant burden on the social and marital life. Here, we assessed the divorce rate and changes in marital status among a sample of Iranian individuals with SCI. METHODS: Referred patients to Brain and Spinal Cord Injury Research Center were invited to participate in this cross-sectional investigation. The Main exclusion criteria were coincidental brain injury, history of chronic diseases before SCI and substance use. Demographic characteristics (including age, gender, educational level, marital status before and after injury and duration of marriage) and Injury characteristics (level of the injury, American spinal injury association (ASIA) scale and Spinal cord independence measure III (SCIM)) were collected. RESULTS: Total of 241 subjects with SCI participated in this investigation (164 (68%) male and 77 (32%) female). Among men, 16.5% [95% CI: 10.81%-22.18%] and among women 18.2% [95% CI: 9.58%-26.81%] got divorced after injury. Duration of marriage before injury was significantly related to lower divorce rate (P< 0.001 and 0.016 in men and women, respectively). Injury characteristics had no relationship with marital longevity. Age was a protective factor against marital dissolution only in men (P< 0.004). CONCLUSION: Our study revealed the divorce rate of 17% [95% CI: 13%-20.9%] after SCI in a sample of Iranian population. The protective influence of age in maintenance of marriage was only detected in men, which proposes existence of a sexual polymorphism in the role of age. Divorce rate was similar between two genders and injury characteristics were not related to divorce rate as well.

Disease-Related Variables and Depression Among Iranian Patients with Parkinson Disease.

BACKGROUND: The factors affecting the correlation between Parkinson disease (PD) and depression have remained unclear. OBJECTIVES: We assessed the prevalence of depression among patients with PD and the association between PD-related variables and depression severity. PATIENTS AND METHODS: This is a cross-sectional study performed in Kermanshah Province of Iran. Sampling was based on recruitment of subjects according to inclusion and exclusion criteria. Patients with confirmed Parkinson disease who were referred to clinics of Kermanshah University of Medical Sciences participated in this study. Depression was evaluated with Beck Depression Inventory-II (BDI-II). Clinical characteristics of PD, including tremor, rigidity, impaired posture, loss of autonomic movement, changes in speech and handwriting, masked face, and hyposmia were indexed. Anhedonia was assessed with Farsi version of Snaith-Hamilton Pleasure Scale. Data were collected between April 2010 and March 2014. RESULTS: A total of 350 patients (52.9% men and 47.1% women) participated in this investigation. Female gender (36.5% in women vs. 13.0% in men, P < 0.0001), impaired posture (27.2% in affected individuals vs. 18.8%, P = 0.002), masked face (39.0% vs. 5.2%, P < 0.0001), and hyposmia (48.7% vs. 21.0%, P = 0.001) were associated with higher susceptibility to profound depression. Lower scores of all domains of Farsi version of Snaith-Hamilton Pleasure Scale (including interest/pastimes, social interaction, sensory experience, and food/drink) were related to more severe depression (P < 0.0001 for all subscales). Severe and profound depression was found in 44% of the participants. CONCLUSIONS: This study estimated that the prevalence of major depression among Iranian individuals with PD living in Kermanshah as 44%. Major determinants of depression were female gender, rigidity, impaired posture, masked face, hyposmia, and anhedonia.

The Risk of Repetition of Attempted Suicide Among Iranian Women with Psychiatric Disorders as Quantified by the Suicide Behaviors Questionnaire.

OBJECTIVES: The factors associated with repetition of attempted suicide are poorly categorized in the Iranian population. In this study, the prevalence of different psychiatric disorders among women who attempted suicide and the risk of repetition were assessed. METHODS: Participants were women admitted to the Poisoning Emergency Hospital, Kermanshah University of Medical Sciences following failed suicide attempts. Psychiatric disorders were diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptom checklist. Risk of repetition was evaluated using the Suicide Behaviors Questionnaire-Revised (SBQ-R). RESULTS: About 72% of individuals had a SBQ-R score >8 and were considered to be at high risk for repeated attempted suicide. Adjustment disorders were the most common psychiatric disorders (40.8%). However, the type of psychiatric disorder was not associated with the risk of repetition (p=0.320). Marital status, educational level, employment, substance use, history of suicide among family members, and motivation were not determinant factors for repetition of suicide attempt (p=0.220, 0.880, 0.220, 0.290, 0.350 and 0.270, respectively). Younger women were associated with violent methods of attempted suicide, such as self-cutting, whereas older individuals preferred consumption of poison (p<0.001). Drug overdose was more common among single and married women whereas widows or divorcees preferred self-burning (p=0.004). CONCLUSION: About 72% of patients with failed suicide attempts were at high risk for repeated attempts. Age, marital status, and type of psychiatric disorder were the only determinants of suicide method. Adjustment disorders were the most common psychiatric disorders among Iranian women. However, this did not predict the risk of further attempts.

Depression, Anxiety and Disease-Related Variables and Quality of Life Among Individuals With Systemic Lupus Erythematosus Living in Kermanshah Province, Iran.

BACKGROUND: Health-related quality of life (HRQoL) is affected by numerous variables including depression and anxiety. However, these associations have not yet been described among patients with systemic lupus erythematosus (SLE) and the impact of SLE-related clinical variables remains unknown. OBJECTIVES: In this cross-sectional study, the prevalence of depression and anxiety among Iranian patients with SLE living in Kermanshah province, Iran, has been estimated and the determinants of HRQoL in comparison with healthy subjects have been identified. PATIENTS AND METHODS: Sampling was performed based on recruitment of subjects according to inclusion and exclusion criteria. Systemic lupus erythematosus-related variables including cutaneous manifestations, pericarditis, arthritis, history of seizure and psychosis were recorded. Blood samples were taken to measure antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), Anti-Smith (Anti-SM), anticardiolipin antibody. Matched healthy subjects in demographic characteristics were selected from general population of Kermanshah province, Iran. Depression and anxiety and HRQoL were assessed using the Beck depression inventory-II, Beck anxiety inventory and short-form 36 health survey, respectively. RESULTS: A total of 310 individuals (160 patients with SLE and 150 healthy subjects) participated in this study. The prevalence of depression and anxiety was about 20% among people with SLE, which was noticeably high but not significantly different from healthy individuals. More severe depression was associated with lower scores in domains of physical functioning (PF), role limitation due to physical problems (RP) and subsequently physical component summary (PCS) in the SLE group (P < 0.0001 for all). A higher anxiety level was negatively correlated with PF, RP, social functioning (SF), general health (GH) and PCS in the SLE group (P = 0.01, < 0.0001, 0.004, 0.02 and 0.005, respectively). Scores of PF and PCS were significantly lower among patients with SLE compared to the control group (P = 0.001 for both). Malar rash, photosensitivity, discoid rash, pleuritis, pericarditis, history of seizure and positive Anti-SM Ab were associated with poorer SF (P = 0.003, 0.003, 0.018, 0.001, < 0.0001, 0.021 and 0.002, respectively). CONCLUSIONS: The results of this study show that patients with SLE have poorer HRQoL in physical components whereas the mental component of QoL is relatively similar to healthy individuals. Depression and anxiety were not related to clinical manifestations of SLE. However, the SF domain of HRQoL was the most susceptible component of QoL, which was affected by SLE clinical variables. The high estimated prevalence of depression and anxiety among patients with SLE requires attention.