Lower Nadir Research Articles

4400 Low CD4 nadir linked to widespread cortical thinning in adults with HIV

OBJECTIVES/GOALS: The history of immune suppression, especially CD4 nadir, has been shown to be a strong predictor of HIV-associated neurocognitive disorders (HAND). However, the potential mechanism of this association is not well understood. This study examined the relationship between CD4 nadir and brain atrophy. METHODS/STUDY POPULATION: Fifty-nine people with HIV participated in the cross-sectional study (mean age, 56.5 ± 5.8; age range, 41-69; 15 females; 46 African-Americans). High resolution structural MRI images were obtained using a 3T Siemens scanner. From a comprehensive 7-domain neuropsychological test battery, a global deficit score (GDS) and HAND diagnoses were determined for each participant. The correlation between CD4 nadir (the lowest ever lymphocyte CD4 count) and cortical thickness was investigated using a vertex-wise non-parametric approach with a conservative statistical threshold of p < 0.05 (FWE-corrected). RESULTS/ANTICIPATED RESULTS: Out of the 59 participants, 12 met standard Frascati criteria for asymptomatic neurocognitive impairment (ANI) and two met the criteria for mild neurocognitive disorder (MND). Across all participants, low CD4 nadir was associated with widespread cortical thinning, especially in the frontal and temporal regions. Higher GDS (indicating worse global neurocognitive function) was associated with bilateral frontal cortical thinning, and the association largely persisted in the subset of participants who did not meet HAND criteria. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest that the low CD4 nadir may be associated with widespread neural injury in the brain, especially in the frontal and temporal regions. This spatial profile might contribute to the prevalence/phenotypes of HAND in the cART era, such as the frequently observed deficits in the executive domain.

164-LB: Lower Pediatric HbA1c in Sweden during Recent Years Is Associated with a Lower HbA1c Nadir during the First Year after Onset

Background: There is a large variation in mean HbA1c levels even between high-income countries, with a decrease over time in HbA1c in some countries but an increase in others. Sweden has experienced a steady decrease in HbA1c over the past 10 years. The aim of this study was to illustrate how changes in HbA1c during the first two years after diagnosis in children and adolescents is related to calendar year for diagnosis of type 1 diabetes from 2010 to 2017. Methods:The Swedish SWEDIABKIDS registry collects data every ~3 months and has > 95% coverage up to age 18 years. We plotted all available HbA1c data vs. diabetes duration, presented as separate Loess curves per 2 consecutive year groups. Results: In total, 5,102 patients contributed with 51,550 HbA1c values over 8 years. HbA1c at onset has slightly increased from 93.9 to 95.0 mmol/mol (10.7 to 10.8 %) between 2010 and 2017. The HbA1c nadir (lowest level during first year) is around 4 months, and has become lower over the years. Early HbA1c tracking is apparent and is established with a difference between the groups from 1 year’s diabetes duration. Conclusions: Intensification of early diabetes treatment, resulting in a lower HbA1c nadir at 4 months and lower HbA1c from 1 year onwards is related to HbA1c two years after diagnosis. Thus, a modifiable factor for a long-term improvement in metabolic control has been identified. Disclosure R. Hanas: Advisory Panel; Self; Abbott, Novo Nordisk A/S. Speaker’s Bureau; Self; Sanofi. Other Relationship; Self; AstraZeneca. I.I. Steineck: None. J. Anderzén: None. K. Eeg-Olofsson: None. J. Ekelund: Employee; Spouse/Partner; AstraZeneca. S. Gudbjörnsdottir: None. L. Hanberger: None. J. Nåtman: None. A. Pundziute Lyckå: None. A. Svensson: None. S. Särnblad: Advisory Panel; Self; Novo Nordisk A/S. Other Relationship; Self; Novo Nordisk A/S. K. Akesson: None.

Thrombocytopenia and its association with mortality in patients with COVID‐19

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes novel coronavirus disease 2019 (COVID‐19), is spreading rapidly around the world. Thrombocytopenia in patients with COVID‐19 has not been fully studied. ObjectiveTo describe thrombocytopenia in patients with COVID‐19. MethodsFor each of 1476 consecutive patients with COVID‐19 from Jinyintan Hospital, Wuhan, China, nadir platelet count during hospitalization was retrospectively collected and categorized into (0, 50], (50, 100], (100‐150], or (150‐) groups after taking the unit (×109/L) away from the report of nadir platelet count. Nadir platelet counts and in‐hospital mortality were analyzed. ResultsAmong all patients, 238 (16.1%) patients were deceased and 306 (20.7%) had thrombocytopenia. Compared with survivors, non‐survivors were older, were more likely to have thrombocytopenia, and had lower nadir platelet counts. The in‐hospital mortality was 92.1%, 61.2%, 17.5%, and 4.7% for (0, 50], (50, 100], (100‐150], and (150‐) groups, respectively. With (150‐) as the reference, nadir platelet counts of (100‐150], (50, 100], and (0, 50] groups had a relative risk of 3.42 (95% confidence interval [CI] 2.36‐4.96), 9.99 (95% CI 7.16‐13.94), and 13.68 (95% CI 9.89‐18.92), respectively. ConclusionsThrombocytopenia is common in patients with COVID‐19, and it is associated with increased risk of in‐hospital mortality. The lower the platelet count, the higher the mortality becomes.

Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort

BackgroundInformation about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid.MethodsIn this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19.Findings51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3–2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per μL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts.InterpretationHIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population.FundingNone.

0675 Nocturnal Oxygen Supplementation With Positive Airway Pressure Therapy For Obesity Hypoventilation Syndrome: Clinical Predictors And Liberation From Oxygen

Abstract Introduction Obesity hypoventilation syndrome (OHS) is associated with a high morbidity and mortality. Many patients require nocturnal supplemental oxygen on top of positive airway pressure (PAP) therapy for hypoxemia independent of apneic events. We need to clinically identify patients likely to require nocturnal oxygen supplementation. Follow up is essential as with adequate control of sleep apnea, hypoxia improves and liberation from nocturnal oxygen supplementation may be achievable. Methods Researchers obtained a list of patients with coding diagnosis of OHS, seen at the Jefferson Sleep Center between November 2016 and September 2019. Patients with BMI of ≥ 30 and evidence of hypoventilation were included. Hypoventilation was defined as an elevated CO2 level of ≥ 45 mmHg on blood gas analysis, elevated serum bicarbonate level of ≥ 27 mmol/L or by evidence of nocturnal hypoventilation by AASM criteria on polysomnography. Patients with pulmonary and neuromuscular disorders were excluded Results Out of 189 patients reviewed, 36 met the inclusion and exclusion criteria. Nineteen patients (53%) required nocturnal oxygen supplementation. A higher serum bicarbonate level of 33 mmol/L against 30 mmol/L (p=0.0078) and a lower resting awake SaO2 of 89% versus 95% (p <0.01) were observed in the oxygen supplementation group. In polysomnographic data, the oxygen supplementation group had lower SaO2 nadir of 67% versus 73% (p=0.026) and had a longer time with SaO2 <88% at 238.2 minutes versus 65.5 minutes (p <0.01). Nine out of the 19 patients (47%) underwent nocturnal oximetry on PAP and room air. Of these, 4 patients (44%) were liberated from oxygen. Conclusion Fifty three percent of patients with OHS required nocturnal oxygen supplementation on top of PAP therapy. Higher serum bicarbonate level and lower resting awake SaO2 are potential clinical predictors of nocturnal oxygen supplementation. After nocturnal oximetry on PAP, 44% were successfully liberated from supplemental oxygen. Support

Hyperlactatemia in diabetic ketoacidosis is common and can be prolonged: lactate time-series from 25 intensive care admissions.

Hyperlactatemia is a documented complication of diabetic ketoacidosis (DKA). Lactate responses during DKA treatment have not been studied and were the focus of this investigation. Blood gas and electrolyte data from 25 DKA admissions to ICU were sequenced over 24h from the first Emergency Department sample. Hyperlactatemia (> 2mmol/L) was present in 22 of 25 DKA presentations [mean concentration = 3.2mmol/L]. In 18 time-series (72%), all concentrations normalized in ≤ 2.6h (aggregate decay t1/2 = 2.29h). In the remaining 7 (28%), hyperlactatemia persisted > 12h. These were females (P = 0.04) with relative anemia (hemoglobin concentrations 131 v 155g/L; P = 0.004) and lower nadir glucose concentrations (5.2 v 8.0mmol/L, P = 0.003). Their aggregate glucose decay curve commenced higher (42mmol/L v 29mmol/L), descending towards a lower asymptote (8mmol/L v 11mmol/L). Tonicity decay showed similar disparities. There was equivalent resolution of metabolic acidosis and similar lengths of stay in both groups. Hyperlactatemia is common in DKA. Resolution is often rapid, but high lactates can persist. Females with high glucose concentrations corrected aggressively are more at risk. Limiting initial hyperglycemia correction to ≥ 11mmol/L may benefit.

Malaria in HIV-infected patients in a nonendemic setting.

The impact of HIV infection on malaria is unclear in nonendemic areas. In endemic territories, HIV has been reported to be a risk factor for higher morbidity. Nowadays, as HIV-infected patients travel more, it is important to assess the impact of HIV at the individual level on imported malaria. This retrospective case-control study collected data on HIV-infected patients diagnosed with malaria (2000-2017) and matched them with two controls based on age, sex and ethnicity. Clinical and biological parameters were collected and compared. We identified 47 cases and matched them with 94 controls. Comparing each of the WHO 2014 severity criteria, hyperparasitemia above 10% (P = 0.006; 12.8 versus 1.1%), icterus (P = 0.042; 14.9 versus 4.3%), acute renal failure (P = 0.022; 25.5 versus 9.6%) and bacteraemia (P = 0.014; 6.4 versus 0%) were significantly more present in HIV-infected patients with a trend to more cerebral malaria (12.8 versus 6.4%). HIV- infected patients were hospitalized more frequently and for longer periods. We observed a higher number of severity criteria when CD4 T-cell count was lower, especially below 200 cells/μl. The difference in occurrence of severe malaria disappeared when patients with CD4 T-cell count more than 500 cells/μl and undetectable viral load (n = 9) were compared with controls. De-novo HIV diagnosis was made during the malaria episode in 17% of cases. HIV infection has an impact on the imported malaria profile, although it is unclear whether well controlled HIV-infected patients have a higher risk of severe malaria. HIV-infected patients should be particularly targeted for pretravel advice.

Relationships Between Chemoreflex Responses, Sleep Quality, and Hematocrit in Andean Men and Women.

Andean highlanders are challenged by chronic hypoxia and many exhibit elevated hematocrit (Hct) and blunted ventilation compared to other high-altitude populations. While many Andeans develop Chronic Mountain Sickness (CMS) and excessive erythrocytosis, Hct varies markedly within Andean men and women and may be driven by individual differences in ventilatory control and/or sleep events which exacerbate hypoxemia. To test this hypothesis, we quantified relationships between resting ventilation and ventilatory chemoreflexes, sleep desaturation, breathing disturbance, and Hct in Andean men and women. Ventilatory measures were made in 109 individuals (n = 63 men; n = 46 women), and sleep measures in 45 of these participants (n = 22 men; n = 23 women). In both men and women, high Hct was associated with low daytime SpO2 (p < 0.001 and p < 0.002, respectively) and decreased sleep SpO2 (mean, nadir, and time <80%; all p < 0.02). In men, high Hct was also associated with increased end-tidal PCO2 (p < 0.009). While ventilatory responses to hypoxia and hypercapnia did not predict Hct, decreased hypoxic ventilatory responses were associated with lower daytime SpO2 in men (p < 0.01) and women (p < 0.009) and with lower nadir sleep SpO2 in women (p < 0.02). Decreased ventilatory responses to CO2 were associated with more time below 80% SpO2 during sleep in men (p < 0.05). The obstructive apnea index and apnea-hypopnea index also predicted Hct and CMS scores in men after accounting for age, BMI, and SpO2 during sleep. Finally, heart rate response to hypoxia was lower in men with higher Hct (p < 0.0001). These data support the idea that hypoventilation and decreased ventilatory sensitivity to hypoxia are associated with decreased day time and nighttime SpO2 levels that may exacerbate the stimulus for erythropoiesis in Andean men and women. However, interventional and longitudinal studies are required to establish the causal relationships between these associations.

Relationship between biochemical and symptomatic hypoglycemia after RYGB. Responses to a mixed meal test: a case-control study.

Postprandial hypoglycemia is a relatively common complication after Roux-en-Y gastric bypass (RYGB). The cause remains incompletely understood, and the association between biochemical hypoglycemia and hypoglycemic symptoms is unclear. To evaluate the association between postprandial hormonal responses and biochemical and symptomatic hypoglycemia after RYGB. University Hospital, Denmark. A case-control study with 3 groups: (1) RYGB group with postprandial hypoglycemic symptoms (HS), n = 13; (2) RYGB-group with no symptoms of hypoglycemia (NHS), n = 13; and (3) nonoperated body mass index-matched controls (CON), n = 7. Plasma glucose (PG) and hormonal responses (insulin, glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon) were measured after a mixed meal test (MMT), and hypoglycemic symptoms were determined by a questionnaire. The primary outcomes were differences in subjective and biochemical responses related to hypoglycemia among the 3 groups. Nadir PG was lower (3.1 versus 4.0 mmol/L (56 versus 72 mg/dL); P = .0002) and peak insulin higher in HS than NHS patients (1073 versus 734 pmol/L; P = .0499). Of the 13 patients with a peak insulin >850 pmol/L, 8 patients developed symptoms whereas only 2 out of the 13 patients with peak insulin ≤850 pmol/L developed symptoms, corresponding to an odds ratio of 12 (1.8; 81.7). Post hoc analyses comparing all RYGB patients with biochemical hypoglycemia after the MMT (nadir glucose ≤3.0 mmol/L [54 mg/dL]) with those with glucose >3 mmol/L (54 mg/dL) revealed a difference in both peak insulin (1138 versus 760 pmol/L; P = .042) and peak glucagon-like peptide-1 (182 versus 86 pmol/L; P = .016) concentrations. Patients with HS had lower nadir PG and higher insulin responses than NHS patients after MMT. Regarding PG, PG ≤3.0 mmol/L (54 mg/dL) was the best discriminator of having hypoglycemic symptoms after the MMT. However, high insulin level seems the most important predictor for having both biochemical and symptomatic hypoglycemia.

Prolonged Amenorrhea and Low Hip Bone Mineral Density in Women Living With HIV-A Controlled Cross-sectional Study.

Women living with HIV (WLWH) have higher rates of prolonged secondary amenorrhea (no flow for ≥1 year) than HIV-negative women. Both having amenorrhea and being HIV positive are associated with lower areal bone mineral density (BMD). However, their combined BMD effects remain unclear. Therefore, we investigated prolonged amenorrhea and BMD in WLWH and controls. This cross-sectional study enrolled WLWH and HIV-negative control women aged 19-68 years of similar backgrounds. We assessed BMD (Hologic; as age- and ethnicity-matched Z-scores) in the Children and women: AntiRetrovirals and Markers of Aging cohort. Participants were stratified by amenorrhea history defined as past/present lack of menses for ≥1 year at age 45 and younger and not because of surgery, breastfeeding, pregnancy, or hormonal contraception. Hip and spine Z-scores by amenorrhea/no amenorrhea used linear models with multivariable analysis for relationships within WLWH. WLWH (N = 129) were similar to controls (N = 129) in age, body mass index, ethnicity, and substance use. Among WLWH, 21% experienced prolonged amenorrhea vs. 9% in controls. WLWH had significantly lower total hip (mean ± SD: -0.4 ± 0.9 vs. 0.3 ± 1.1; P < 0.001) and spine (-0.5 ± 1.3 vs. 0.2 ± 1.3; P = 0.001) Z-scores than controls. Amenorrhea was independently associated with hip (P = 0.01) but not spine (P = 0.94) BMD by multivariable linear regression. WLWH with amenorrhea had lower hip Z-scores (-0.8 ± 0.9) than those without (-0.3 ± 0.8; P = 0.01). They also had higher rates of substance use, smoking, opioid therapy, hepatitis C coinfection, and lower CD4 nadir. WLWH had higher rates of prolonged amenorrhea and lower BMD than controls. WLWH with amenorrhea experienced lower hip BMD Z-scores than those without. Prolonged amenorrhea is an added osteoporosis risk in WLWH.

Lung function in men with and without HIV.

Initial studies suggest HIV-positive persons may be at increased risk for chronic lung diseases such as chronic obstructive pulmonary disease, but have commonly relied on single-center designs, lacked HIV-negative controls, or assessed lung function with only spirometry. We tested differences in spirometry and single-breath diffusing capacity for carbon monoxide (DLCO) in persons with and without HIV. Cross-sectional, observational study. Participants were enrolled from the Multicenter AIDS Cohort Study, a longitudinal cohort study of men who have sex with men (both HIV-positive and HIV-negative) at four sites in the United States. Standardized spirometry and DLCO testing were performed in all eligible, consenting participants at routine study visits. We tested associations between HIV status and spirometry and DLCO results, using linear and logistic regression. Among 1067 men, median age was 57 years, prevalence of current marijuana (30%), and cigarette (24%) use was high, and another 45% were former cigarette smokers. Median forced expiratory volume in 1 s was 97% of predicted normal and DLCO was 85% of predicted normal. HIV-positive persons demonstrated no statistical difference in forced expiratory volume in 1 s compared with HIV-negative persons, but had worse DLCO (adjusted difference -2.6% of predicted; 95% confidence interval: -4.7 to -0.6%) and a higher risk of DLCO impairment (odds ratio for DLCO < 60% of predicted 2.97; 95% confidence interval: 1.36-6.47). Lower DLCO was associated with lower nadir CD4 cell counts. HIV-positive men are at increased risk of abnormal gas exchange, indicated by low DLCO, compared with men without HIV.

Mean cardiopulmonary dose and vertebral marrow dose differentially predict lineage-specific leukopenia kinetics during radiotherapy for esophageal cancer

Background and purposeLymphopenia is associated with poor outcomes in esophageal cancer (EC) patients undergoing chemoradiotherapy (CRT). We hypothesized that radiation dose to marrow (central) vs. circulating (peripheral) leukocytes (WBCs) may have unique effects on WBC counts and clinical outcomes in EC. Materials and methodsWeekly and 90-day post-CRT blood cell counts were evaluated for 46 patients with stage II-III EC treated with CRT. Thoracic vertebral volume spared (TVS) radiation was extracted from dose volume histograms (DVH). Mean cardiopulmonary dose (mCPD) was calculated as mean dose to the volumetric sum of heart, lungs, and great vessels as a surrogate for circulating blood pool. Linear and logistic regression identified associations between dosimetric variables and hematologic toxicities (HT). Repeated measures ANOVA tested associations between cell count trends and clinical predictors. ResultsWBCs and platelets reached nadir at week 6 of CRT. On multivariate analysis, mCPD was associated with lower WBC and neutrophil nadirs (p < 0.05). TVS5-40 Gy were associated with higher lymphocyte nadirs (all p < 0.05). Repeated measures ANOVA revealed an interaction effect of sex on absolute lymphocyte trend as well as age (<67 vs. >67) and diabetes on normalized lymphocyte trend (all p < 0.015). ConclusionsmCPD and volume of thoracic marrow spared radiation differentially predict lineage-specific leukopenias during CRT for EC. mCPD is significantly associated with lower total WBC and neutrophil nadirs. In contrast, greater thoracic marrow spared radiation is associated with mitigation of lymphopenia during CRT. Clinical factors such as sex, age, and diabetes may be associated with a more rapid decline in hematologic counts during treatment.

Characterization of serum levels of testosterone and corticosterone in a blast and amputation rat model of heterotopic ossification

IntroductionEndocrine dysregulation's role in heterotopic ossification (HO) remains unexplored. We sought to examine corticosterone and testosterone in established rat models of ectopic bone formation, and correlate to HO formation with CT analysis. MethodsFifteen rats were placed into three groups of traumatic injury patterns: Blast and injury (120 kPa blast, femoral fracture and quadriceps crush), injury only, and blast only. Serum corticosterone and testosterone levels were drawn until post-operative day 40. HO was analyzed using CT. ResultsCorticosterone levels peaked in the blast and injury group in the shortest time post injury, followed by injury only and blast only groups. Testosterone levels reached nadir in similar fashion. Volume of HO was highest in the blast and injury group, followed by the injury only group. ConclusionCorticosterone and testosterone's contribution to HO formation requires further characterization, but this study suggests that high peaks in corticosterone and a low nadir in testosterone are associated with higher volumes of HO.

Biomarkers of prolonged time to treatment failure in metastatic castration-resistant prostate cancer patients treated with abiraterone or enzalutamide: A real life patients-based nomogram and web app.

202 Background: Survival outcomes for metastatic castration resistant prostate cancer (mCRPC) patients (pts) have greatly improved following the approval of Docetaxel and abiraterone(Abi)/enzalutamide(Ez). However, it is not clear who is likely to benefit more from these therapies in real life clinical practice. Methods: A retrospective cohort study was performed with mCRPC pts treated with Abi/Ez in pre-Docetaxel setting. Primary endpoint: to identify predictive biomarkers of long time to treatment failure (TTF), develop a nomogram and convert it into a web app. Secondary endpoint: to correlate biomarkers with overall survival (OS). Kaplan Meier survival estimates and Cox Regression models were used for time-to-event analyses. Statistical analysis was made with R software. All statistical tests were two-sided and statistical significance was fixed at 0.05. Results: From May2012 to October2017, 117 pts were assessed, 81 received Abi and 36 Ez. Median follow-up of 21 months (mo), estimated median TTF was 12.8mo (95%CI 9.98-15.7) for the total population. Predictive biomarkers for TTF included in the first nomogram model were time from start of androgen deprivation therapy (tADT) to start of Abi/Ez, pain at baseline, Gleason score, baseline testosterone and lower PSA nadir in castration sensitive prostate cancer (CSPC). The second nomogram model included pain and Gleason plus neutrophil counts, tADT to CRPC and baseline PSA at CRPC. C-index: 0.726 and 0.731 respectively, providing a reliable prediction of long-term benefit with Abi/Ez in this setting. All these characteristics were significantly associated with OS. Conclusions: The two nomogram achieved a good internal validation and can work as a tool to the decision-making process of the best strategy to first-line therapy in mCRPC pts.[Table: see text]

Association of salvage cryoablation with decreased utilization of androgen deprivation therapy for recurrent prostate cancer after radiotherapy.

358 Background: Cryoablation is an established treatment for recurrent prostate cancer after primary radiotherapy, but outcomes data are mostly limited to uncontrolled case series. We assessed salvage cryoablation efficacy with a comparative analysis in a large national cohort. Methods: Patients with clinically localized prostate cancer treated with primary radiotherapy from 2000 to 2015 were identified in the Veterans Affairs Informatics and Computing Infrastructure (VINCI) dataset. Prostate-specific antigen (PSA) recurrence was defined as nadir + 2 ng/mL. Inclusion criteria included availability of serial PSA measures for ≥ 3 years after completion of radiotherapy and PSA &lt; 10 ng/mL at recurrence. Salvage cryotherapy was identified with procedure- and fee-based billing codes. Chi square and Wilcoxon analysis was utilized for descriptive statistics; and Kaplan Meier analyses for time to androgen deprivation therapy (ADT). Results: Among 35,502 patients who underwent primary radiotherapy, 4,391 (12.3%) developed biochemical recurrence a median (IQR) of 4.5 (2.7, 6.9) years after treatment. Of these, 3889 (88.9%) had PSA &lt; 10 ng/mL at time of recurrence, of whom 95 (2.4%) underwent salvage cryoablation. Cryoablation patients were younger at initial diagnosis (60 years versus 65 years, p &lt; 0.01); had a lower pre-treatment PSA (6.6 ng/mL versus 7.8 ng/mL, p &lt; 0.01); and had a lower PSA nadir (0.04 ng/mL versus 0.19 ng/mL, p&lt;0.01). There were no between-group differences for clinical stage at initial diagnosis (p = 0.22) or African American prevalence (34.7% versus 29%, p =0.27). After recurrence, median (IQR) follow-up for those who did and did not receive cryoablation was 9.1 (7.2, 9.11) and 8.1 (5.4, 10.9) years, respectively. Cryoablation patients were less likely to receive ADT (40% versus 55%, p &lt; 0.01); and, among those who did, time to ADT from recurrence was significantly longer compared to those who did not receive cryoablation (15.5 months versus 5.8 months, p&lt;0.01). Conclusions: Salvage cryoablation is associated with decreased utilization of ADT in patients with biochemical recurrence after radiation.

Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer.

241 Background: It is unknown whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration resistant prostate cancer (mCRPC) patients. Methods: We reviewed the Michinoku Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW) adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis. Results: Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir &gt;0.64 ng/mL and TTN &lt;7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC and CRPC-free survival. The Cox proportional and IPTW-adjusted multivariate analyses revealed that the unfavorable group had a negative impact on OS in mCRPC patients (hazards ratio [HR] 2.98, P &lt; 0.001). Conclusions: Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.[Table: see text]

Effects of storage time prolongation on in vivo and in vitro characteristics of 4°C-stored platelets.

Cold (4°C)-stored platelets are currently under investigation for transfusion in bleeding patients. It is currently unknown how long cold-stored platelets can be stored for clinical applications. Twenty three subjects were recruited. Twenty-one subjects were available for in vivo assessment and received indium-111 radiolabeled, cold-stored platelets. We investigated 5- (n = 5), 10- (n = 6), 15- (n = 5), and 20-day-stored (n = 5) platelets and obtained samples for in vitro testing at baseline and after the designated storage time. Twenty three units were available for in vitro testing. Five- and 7-day (n = 5 each), room temperature (RT)-stored platelets served as the current clinical standard control. In vivo, we found a continuous decline in platelet recovery from 5 to 20 days. Platelet survival reached a low nadir after 10 days of storage. Ex vivo, we observed the maximum platelet αIIbβ3 integrin response to collagen at 5 days of cold storage, and we saw a continuous decline thereafter. However, platelet integrin activation and mitochondrial membrane integrity were better preserved after 20 days at 4°C, compared to 5 days at RT. Platelet metabolic parameters suggest comparable results between 20-day cold-stored platelets and 5- or 7-day RT-stored platelets. In summary, we performed the first studies with extended, cold-stored, apheresis platelets in plasma for up to 20 days with a fresh comparator. Storing cold-stored platelets up to 20 days yields better results in vitro, but further studies in actively bleeding patients are needed to determine the best compromise between hemostatic efficacy and storage prolongation.

Are genotype and biomarkers enough to initiate enzyme replacement therapy in Fabry disease? The value of the biopsy

Management of symptoms and prevention of life-threatening hemorrhage in immune thrombocytopenia (ITP) must be balanced against adverse effects of therapies. Because current treatment guidelines based on platelet count are confounded by variable bleeding phenotypes, there is a need to identify new objective markers of disease severity for treatment stratification. In this cross-sectional prospective study of 49 patients with ITP and nadir platelet counts <30 × 109/L and 18 aged-matched healthy controls, we used susceptibility-weighted magnetic resonance imaging to detect cerebral microbleeds (CMBs) as a marker of occult hemorrhage. CMBs were detected using a semiautomated method and correlated with clinical metadata using multivariate regression analysis. No CMBs were detected in health controls. In contrast, lobar CMBs were identified in 43% (21 of 49) of patients with ITP; prevalence increased with decreasing nadir platelet count (0/4, ≥15 × 109/L; 2/9, 10-14 × 109/L; 4/11, 5-9 × 109/L; 15/25 <5 × 109/L) and was associated with longer disease duration (P = 7 × 10−6), lower nadir platelet count (P = .005), lower platelet count at time of neuroimaging (P = .029), and higher organ bleeding scores (P = .028). Mucosal and skin bleeding scores, number of previous treatments, age, and sex were not associated with CMBs. Occult cerebral microhemorrhage is common in patients with moderate to severe ITP. Strong associations with ITP duration may reflect CMB accrual over time or more refractory disease. Further longitudinal studies in children and adults will allow greater understanding of the natural history and clinical and prognostic significance of CMBs.

Anti-inflammatory medications for obstructive sleep apnoea in children.

Anti-inflammatory medications for obstructive sleep apnoea in children.

Dual kidney transplantation offers a safe and effective way to use kidneys from deceased donors older than 70 years

PurposeDual kidney transplantation (DKT) offers a way to extend the use of kidneys from expanded criteria donors (ECDs). Here, we compared the outcomes of DKT with those of single kidney transplantation from standard criteria donors (SCDs) and ECDs.MethodsIn 2014, we began performing DKT using both kidneys from deceased donors greater than 70 years of age with one of two risk factors: serum creatinine (sCr) level over 3.0 mg/dl or eGFR under 30 ml/min. By 2017, we had performed 15 DKTs. We compared the outcomes of the 15 DKT recipients with those of 124 patients who received a kidney from an SCD and 80 patients who received a kidney from an ECD.ResultsCompared with ECDs and SCDs, DKT donors were older, had a higher diabetes burden, and a higher sCr level (p < 0.01, < 0.01, and 0.03, respectively). DKT recipients were also older and had a higher diabetes burden than recipients of kidneys from ECDs and SCDs (p < 0.01, both). DKT recipients had a lower nadir sCr and shorter duration to nadir sCr than single ECD KT recipients (p < 0.01and 0.04, respectively).ConclusionsThe survival rates of DKT grafts were compatible with those of single KT grafts. Therefore, DKT may be considered a suitable an option to expand the donor pool.