Association of Psychosocial Factors with Activation Among Patients with Glaucoma.

OBJECTIVE: To investigate the association of psychosocial factors with health self-management behaviors and beliefs among patients with primary open-angle glaucoma (POAG). DESIGN: Prospective cross-sectional cohort study. PARTICIPANTS: Patients (n = 202) with mild, moderate, or advanced bilateral POAG. METHODS: Patients (N = 1164) were identified from electronic medical records at a single academic medical center. Letters soliciting participation were mailed to 591 randomly selected potential participants. Psychometric measures and a social determinants of health questionnaire were administered by phone to 202 study participants. MAIN OUTCOME MEASURES: The National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ), the Multidimensional Health Locus of Control (MHLC), the Perceived Medical Condition Self-Management Scale-4, the Patient Health Questionnaire-9 (PHQ), the Patient Activation Measure-13 (PAM), a health literacy question, and a social determinants of health questionnaire. RESULTS: For each increase in level of POAG severity, there was a decrease in mean NEI-VFQ score (P < 0.001). For each unit increase in NEI-VFQ item 1, self-rated vision, mean PAM score increased (R2 = 5.3%; P = 0.001; 95% confidence interval [CI], 0.077-0.276). For each unit increase in "Internal" on the MHLC, mean PAM score increased (R2 = 19.3%; 95% CI, 0.649-1.166; P < 0.001). For each unit increase in "Doctors" on the MHLC, mean PAM score increased (R2 = 11.0%; 95% CI, 1.555-3.606; P < 0.001). For each unit increase in "Chance" on the MHLC, mean PAM score decreased (R2 = 2.6%; 95% CI, -0.664 to -0.051; P = 0.023). On multivariate analysis, adjusting for age, sex and race, for each unit increase in PHQ, mean PAM score decreased (95% CI, 0.061-1.35; P = 0.032); for each unit increase in MHLC "Doctors", mean PAM score increased (95% CI, -1.448 to 3.453; P < 0.001); for each unit increase in MHLC "Internal", mean PAM score increased (95% CI, 0.639-1.137; P < 0.001); for each unit increase in MHLC "Chance", mean PAM score decreased (95% CI, -0.685 to -0.098; P = 0.009). CONCLUSIONS: We identified modifiable behavioral factors that could increase patients' self-perceived ability and confidence to manage their own eye care. Locus of control (MHLC), level of depression (PHQ), and self-rated functional vision (NEI-VFQ) were each associated with patient behaviors, attitudes, and beliefs needed for health self-management (activation, assessed by the PAM) and may be important determinants of adherence behaviors. Targeting change in patients' care beliefs and behaviors may improve activation and treatment outcomes. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Heterozygous mutations in SOX2 may cause idiopathic hypogonadotropic hypogonadism via dominant-negative mechanisms.

Pathogenic SRY-box transcription factor 2 (SOX2) variants typically cause severe ocular defects within a SOX2 disorder spectrum that includes hypogonadotropic hypogonadism. We examined exome-sequencing data from a large, well-phenotyped cohort of patients with idiopathic hypogonadotropic hypogonadism (IHH) for pathogenic SOX2 variants to investigate the underlying pathogenic SOX2 spectrum and its associated phenotypes. We identified 8 IHH individuals harboring heterozygous pathogenic SOX2 variants with variable ocular phenotypes. These variant proteins were tested in vitro to determine whether a causal relationship between IHH and SOX2 exists. We found that Sox2 was highly expressed in the hypothalamus of adult mice and colocalized with kisspeptin 1 (KISS1) expression in the anteroventral periventricular nucleus of adult female mice. In vitro, shRNA suppression of mouse SOX2 protein in Kiss-expressing cell lines increased the levels of human kisspeptin luciferase (hKiss-luc) transcription, while SOX2 overexpression repressed hKiss-luc transcription. Further, 4 of the identified SOX2 variants prevented this SOX2-mediated repression of hKiss-luc. Together, these data suggest that pathogenic SOX2 variants contribute to both anosmic and normosmic forms of IHH, attesting to hypothalamic defects in the SOX2 disorder spectrum. Our study describes potentially novel mechanisms contributing to SOX2-related disease and highlights the necessity of SOX2 screening in IHH genetic evaluation irrespective of associated ocular defects.

Amenorrhea and Estrogen Disorders in Kidney Disease.

Sexual and reproductive function are impacted negatively in individuals with chronic kidney disease and end-stage renal disease. Disruption of the hypothalamic-pituitary-gonadal axis plays a pivotal role in contributing to these manifestations as a result of decreasing kidney function and the development of uremia. Early menopause is encountered commonly in women with reduced kidney function, and treatment is problematic as a result of reduced kidney function changing the half-life of medications. Kidney transplantation corrects some of these abnormalities, but medications required after transplantation as well as the persistence of other comorbidities are barriers to normal restoration of gonadal dysfunction.

Phenotypic continuum between Waardenburg syndrome and idiopathic hypogonadotropic hypogonadism in humans with SOX10 variants.

PURPOSE: SOX10 variants previously implicated in Waardenburg syndrome (WS) have now been linked to Kallmann syndrome (KS), the anosmic form of idiopathic hypogonadotropic hypogonadism (IHH). We investigated whether SOX10-associated WS and IHH represent elements of a phenotypic continuum within a unifying disorder or if they represent phenotypically distinct allelic disorders. METHODS: Exome sequencing from 1,309 IHH subjects (KS: 632; normosmic idiopathic hypogonadotropic hypogonadism [nIIHH]: 677) were reviewed for SOX10 rare sequence variants (RSVs). The genotypic and phenotypic spectrum of SOX10-related IHH (this study and literature) and SOX10-related WS cases (literature) were reviewed and compared with SOX10-RSV spectrum in gnomAD population. RESULTS: Thirty-seven SOX10-associated IHH cases were identified as follows: current study: 16 KS; 4 nIHH; literature: 16 KS; 1 nIHH. Twenty-three IHH cases (62%; all KS), had ≥1 known WS-associated feature(s). Moreover, five previously reported SOX10-associated WS cases showed IHH-related features. Four SOX10 missense RSVs showed allelic overlap between IHH-ascertained and WS-ascertained cases. The SOX10-HMG domain showed an enrichment of RSVs in disease states versus gnomAD. CONCLUSION: SOX10 variants contribute to both anosmic (KS) and normosmic (nIHH) forms of IHH. IHH and WS represent SOX10-associated developmental defects that lie along a unifying phenotypic continuum. The SOX10-HMG domain is critical for the pathogenesis of SOX10-related human disorders.

BK polyomavirus-pathogen, paradigm and puzzle.

BK virus is a polyomavirus with seroprevalence rates of 80% in adults. Infection is usually acquired during childhood, and the virus is benign or pathologic depending on immune status. The virus reactivates in immunodeficiency states, mostly among transplant (either kidney or bone marrow) recipients. There are approximately 15 000 renal transplants every year in the USA, of which 5-10% develop BK polyomavirus nephropathy; 50-80% of patients who develop nephropathy go on to develop graft failure. BK virus is associated with BK polyomavirus nephropathy, ureteral stenosis, late-onset hemorrhagic cystitis, bladder cancer and other nonlytic large T-expressing carcinomas. The renal spectrum begins with viruria and can end with graft failure. The clinical spectrum and outcomes vary among transplant patients. New noninvasive diagnostic methods, such as urinary polyomavirus Haufen detected by electron microscopy, are currently under study. Treatment is primarily directed at decreasing immunosuppression but may be associated with graft rejection. Repeat transplantation is encouraged as long as viral clearance in plasma prior to transplant is accomplished. There remain no definitive data regarding the utility of transplant nephrectomy.

Successful Salvage of a Renal Allograft after Acute Renal Vein Thrombosis due to May-Thurner Syndrome.

A 68-year-old Caucasian female with a past medical history of a deceased donor kidney transplant four months prior was admitted with a two-day history of anuria and acute kidney injury. A renal ultrasound demonstrated thrombus in the transplanted kidney's renal vein that extended into the left iliac vein as well as into the left femoral venous system. Catheter-guided tissue thrombolytics were infused directly into the clot. Within twelve hours of initiating thrombolytic infusion, there was brisk urine output. Interval venography demonstrated decreasing clot burden. At the time of discharge her creatinine was 0.78 mg/dL, similar to her baseline value prior to presentation. The patient was noted to have May-Thurner syndrome on intravascular ultrasound (IVUS). Angioplasty followed by stent placement was done. Unique to our case report was the timing of the presentation of renal vein thrombosis (four months after transplant) and the predisposing anatomy consistent with May-Thurner syndrome, which was diagnosed with IVUS and successfully treated with local thrombolytics.

AA amyloidosis in the renal allograft: a report of two cases and review of the literature.

AA amyloidosis is a disorder characterized by the abnormal formation, accumulation and systemic deposition of fibrillary material that frequently involves the kidney. Recurrent AA amyloidosis in the renal allograft has been documented in patients with tuberculosis, familial Mediterranean fever, ankylosing spondylitis, chronic pyelonephritis and rheumatoid arthritis. De novo AA amyloidosis is rarely described. We report two cases of AA amyloidosis in the renal allograft. Our first case is a 47-year-old male with a history of ankylosing spondylitis who developed end-stage renal disease reportedly from tubulointerstitial nephritis from non-steroidal anti-inflammatory agent use. A biopsy was never performed. One year after transplantation, AA amyloidosis was identified in the femoral head and 8 years post-transplantation, AA amyloidosis was identified in the renal allograft. He was treated with colchicine and adalimumab and has stable renal function at 1 year-follow-up. Our second case is a 57-year-old male with a long history of intravenous drug use and hepatitis C infection who developed end-stage kidney disease due to AA amyloidosis. Our second patient's course was complicated by renal adenovirus, pulmonary aspergillosis and hepatitis C with AA amyloidosis subsequently being identified in the allograft 2.5 years post-transplantation. Renal allograft function remains stable 4-years post-transplantation. These reports describe clinical and pathologic features of two cases of AA amyloidosis presenting with proteinuria and focal involvement of the renal allograft.