Faculty Bibliography

Background: USD is a preventable disease characterized by significant risk of recurrence. A "cascade of care" shows how many patients are lost to follow-up at diagnosis, referral, and treatment and is a useful tool in delivering HIV care. We can analyze our success, or failure, in the secondary prevention of kidney stones and retention of patients by constructing a cascade of care.
Method(s): We abstracted data from observational studies to identify impediments to care of patients with USD Results: In the US there are about 1.2 million ER visits per year. 37% of patients diagnosed with stones receive a follow-up consultation with a urologist and fewer see a nephrologist. Although 24h urine collection results may decrease stone recurrence rate, only 7.4% do them. 50% of patients experience a recurrent 2nd episode within 5 years. Of these 24% undergo a complete evaluation, 18% are referred to a nephrologist and 13.8% are prescribed medical therapy. 30% remain adherent to this pharmacotherapy. Of patients that are adherent 27% have lower odds of an ER visit than non-adherent patients. The cascade of care demonstrates that a low prevalence of patients receive proper followup. The impediments to the care of patients with kidney stones are (1) the unrecognized comorbidities of stones (2) disconnect between the ER and stone experts and (3) the low prevalence of 24h urine collections and prescribed medical therapy.
Conclusion(s): It is important to identify loci in the cascade of care that could represent opportunities to change practice. Prescription of appropriate fluid therapy and dietary changes and a referral to an expert should 1st be initiated by the ER. The low prevalence of 24h urine collections may reflect that the data are intimidating for some. Empiric therapy for calcium stones with fluids, diet, thiazides and potassium citrate may be a rational therapy to achieve significant supersaturation reductions and could be compared with targeted medical therapy in a randomized controlled trial. A greater effort needs to be devoted to develp a comprehensive flow of participants to retain patients in the cascade of care for USD. (Table Presented)

Background: The assessment of HRQoL in RKSF is important for following disease course and evaluating treatment. Previously, using a non-disease specific instrument we showed that RKSF present differently, with the worst domain scores in cystinuria. These are the first follow-up data based on summary scores for adults in a cross-sectional comparison.
Method(s): RKSF were enrolled from 4 RKSC registries: primary hyperoxaluria, cystinuria, Dent disease and APRTd. HRQoL is measured with the generic non-disease specific SF-36v2. Results are norm-based scores (NBS) based on US Standard Population (Domain score mean = 50). Group means < 47 indicate the presence of impaired functioning in associated dimension.
Result(s): We scored 545 surveys of the adult population at different time points, adjusted for the last stone event and compared the Physical and Mental Component Scores (PCS and MCS). We found the lowest PCS in Dent, and the highest in PH. The lowest MCS was found in cystinuria, the highest was found in PH. Low PCS indicate restrictions in self-care, physical, social and role activities; bodily pain, tiredness and poor rated health. Low MCS are associated with frequent psychological distress, social and role disability due to emotional problems, and poor rated health. Participants with cystinuria reported more stone events with related procedures than other RKSF (X2 (9) 23.375, p=.005).
Conclusion(s): HRQoL in RKSF is influenced by stone events and can be assessed with a non-disease specific SF-36v2. Adjusting for time between the survey and last event allows for the interpretation of more meaningful HRQoL profiles. The time from the last stone event and related procedures affect HRQOL in RKSF significantly. (Table Presented)

Background: Urine chemistry is a determinant of stone formation in cystinuria. We previously showed that positive cystine capacity (CysCap), a measure of higher cystine solubility, led to fewer stone events. We queried the RKSC Cystinuria Registry to determine urinary and medication variables associated with positive (CysCap+), rather than negative (CysCap-) values.
Method(s): This is the 1st report from the Cystinuria Registry, with data on 300 people with cystinuria (142 males, 158 females; age at enrollment 38 +/- 17 years). 112 participants had 306 determinations of CysCap, measured by Litholink (Chicago, IL). In this cross-sectional study we compared variables associated with CysCap+ vs CysCap-.
Result(s): Lower urine Na (r=0.48; Fig 1A) and creatinine (r=0.62, not shown) were associated with lower 24h urine cystine (UC; P<0.001). Increasing CysCap values were seen with increasing urine pH (rs=0.45, Fig 1B), volume (rs=0.44) and decreasing UC (rs=-0.44 Fig 1C; all P<0.001). Dividing Cyscap determinations into CysCap+ and CysCapgroups (Table), only higher urine volume and greater daily citrate doses were different. Relatively few participants were taking citrate or tiopronin.
Conclusion(s): Higher urine pH and volume and lower UC were associated with less lithogenic urine; lower UC was seen with less Na and creatinine. Higher volume and citrate doses distinguished patients with less lithogenic urine. Many patients with cystinuria may be undertreated and would benefit from better dietary adherence. (Table Presented)

Introduction: Patients with pure autonomic failure (PAF) typically present with symptoms of sympathetic insufficiency, with anhidrosis frequently reported. We here report an unusual patient with PAF who presented with cold-induced sweating. Methods: Case report. Results: A 73-year-old man had a 5-year history of frequent lightheadedness, dizziness and syncope on standing. He also had erectile dysfunction, nocturia, constipation, and dream reenactment. He also reported a significant increase in sweating in his torso, back, and both arms (particularly the left) induced by cold temperatures. Autonomic testing showed a supine hypertension (193/105 mmHg) with resting bradycardia (50 bpm). Blood pressure overshoot after release of the Valsalva strain was absent, indicating impaired baroreflex-mediated sympathetic activation. After 14-min of head-up tilt his blood pressure had dropped to 124/83 mmHg with a blunted increase in heart rate to 73 bpm. His norepinephrine levels failed to increase appropriately upon head-up tilt (supine 376 pg/mL; tilted 404 pg/mL), indicating a neurogenic cause for his orthostatic hypotension. Electrochemical skin conductance was reduced in palms and soles. An iodine-starch test was performed with a room temperature of 90degreeF and repeated after the temperature was decreased to 78degreeF. When the ambient temperature was reduced, the starch powder turned dark purple, more intensely in the left side, indicating the release of sweat. Conclusion: Cold-induced sweating can be a manifestation of autonomic failure. Possible mechanisms include cold-induced sudomotor supersensitivity triggered by the remaining fibers innervating the sweat glands

Background: Symptoms of psychosis, including hallucinations and delusions, are relatively frequent in Parkinson disease and Lewy body dementia, particularly in patients receiving levodopa and dopamin-ergic agonists. However, the prevalence of psychosis in multiple system atrophy (MSA) is unknown. We aimed to determine the prevalence and characteristics of psychotic symptoms in patients with MSA, and factors associated with their development. Methods: Consecutive patients with probable MSA without previous history of psychiatric disorders were prospectively enrolled in a longitudinal observational study. The presence of hallucinations and delusions was determined during a standardized clinical interview and quantified with the Scale for the Assessment of Positive Symptoms in Parkinson disease (SAPS-PD). Patients also underwent full evaluation of visual acuity, cognition (Montreal Cognitive Assessment, MoCA), motor function and disease severity [United Multiple System Atrophy Rating Scale (UMSARS)]. Results: Of the 31 consecutive patients with probable MSA (17 men; mean age 64 +/- 8 years; 13 MSA-P and 14 MSA-C), 6 (19%) had positive symptoms of psychosis including delusions and/or hallucinations. All but one patient had the cerebellar phenotype of the disease (MSA-C). Auditory hallucinations occurred in 4 patients, visual hallucinations in 4, persecutory delusions in 3, and jealousy delusions in 3. No patients reported somatic or tactile hallucinations. Psychosis symptoms were extremely severe and refractory to treatment in 2 cases with MSA-C, both of whom died within 12 months of psychosis onset. Psychotic symptoms were not associated with levodopa or other antiparkinsonian medication treatment, visual acuity, cognitive score, depression score, or duration of illness. Conclusions: Psychotic symptoms occur in *20% of patients with MSA, the vast majority of whom have MSA-C. Severe refractory psychotic symptoms appear to be associated with poor prognosis (death < 1 year). Our results suggest that psychotic symptoms in MSA are unrelated to visual system abnormalities

As the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks^®computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey (Macaca fascicularis) visual cortex. The 3-D CAD model of the brain was used to customize an [Formula: see text] Utah optrode array (UOA) after it was determined that a high-density ([Formula: see text]) UOA caused extensive damage to marmoset (Callithrix jacchus) primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.5-mm-diameter through glass via. The [Formula: see text] UOA was customized for optrode length ([Formula: see text]), optrode width ([Formula: see text]), optrode pitch ([Formula: see text]), backplane thickness ([Formula: see text]), and overall form factor ([Formula: see text]). Two [Formula: see text] UOAs were inserted into layer VI of macaque V4D cortices with minimal damage as assessed in fixed tissue cytochrome oxidase staining in nonrecoverable surgeries. Additionally, two [Formula: see text] arrays were implanted in mice (Mus musculus) motor cortices, providing early evidence for long-term tolerability (over 6 months), and for the ability to integrate the UOA with a Holobundle light delivery system toward patterned optogenetic stimulation of cortical networks.

Total N-acetyl-aspartate + N-acetyl-aspartate-glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (1 H-MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%-65% of the brain. Here we wish to demonstrate that non-localized, whole-head (WH) 1 H-MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 +/- 8.5 years old, were recruited and underwent T1 -weighted MRI for tissue segmentation, non-localizing, approximately 3 min WH 1 H-MRS (TE /TR /TI = 5/10/940 ms) and 30 min 1 H-MR spectroscopic imaging (MRSI) (TE /TR = 35/2100 ms) in a 360 cm3 volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 +/- 0.5, 5.5 +/- 0.4 and 1.3 +/- 0.2 mM, were all within 10% of the WH: 8.6 +/- 1.1, 6.0 +/- 1.0 and 1.3 +/- 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the "brain-only" VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 +/- 0.03 (brain approximately 30% of WH volume). Air-tissue susceptibility-driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non-localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH-1 H-MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.