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Context/Aims: Pheochromocytoma and paraganglioma (PPGL) are rare tumors, and data on ambulatory blood pressure monitoring (ABPM) in these patients and the effect of blocking on ABPM parameters is limited. We aimed to describe ABPM parameters in a cohort of PPGL at our center in western India. Methods: Retrospective study of patients with PPGL whose ABPM data was available. Demographic details, secretory status, and ABPM data were retrieved. Coefficient of variability (CV) was calculated as standard deviation/mean in percentage. Results: In the 39 included patients, mean age at presentation was 39.3 ± 14.2 yr; 20 (51.3%) were males, 25 (64.1%) hypertensive, and mean tumor diameter was 5.3 cm. In 18 patients whose baseline ABPM was done without medications, those with nocturnal blood pressure dipping (6/18, 33%) had higher serum metanephrines (median 313.2 vs. 34.7 pg/ml, P = 0.028). Despite normal office blood pressure (BP), 8.9% of systolic BP readings were >140 mmHg, and 1.2% were >160 mmHg. Among 29 patients with both pre and post-block ABPM, mean BP (systolic 121.6 vs. 132.5 mmHg, P = 0.014; diastolic 68.9 vs. 76.4 mmHg, P = 0.005) and percentage of BP readings above 140 mmHg (median 9.4% vs. 24.4%, P = 0.016) were significantly lowered after the preoperative blockade in hypertensive (n = 19) patients, whereas CV was similar. The post-blockade ABPM characteristics were similar in patients blocked with amlodipine or prazosin. Conclusion: ABPM provides additional information about BP characteristics in PPGL. The preoperative blocking decreases the magnitude of BP excursions but does not affect BP variability. [ABSTRACT FROM AUTHOR]

Introduction: Differentiating pheochromocytomas from other adrenal masses based on computed tomography (CT) characteristics remains challenging, particularly in lipid-poor lesions with variable washout patterns. This study evaluated CT features for distinguishing pheochromocytomas in good and poor washout subcohorts., Methods: We prospectively analyzed 72 patients with unilateral lipid-poor adrenal masses. CT protocol included basal, bolus-tracked arterial, early venous (45 seconds postarterial), and delayed (15 minutes postarterial) phases. Masses were categorized into good and poor washout groups. Histopathology provided the final diagnosis. CT characteristics and calculated indices were compared between pheochromocytomas and other masses in each washout category., Results: The cohort included pheochromocytomas (n = 35), adrenocortical carcinoma (ACC; n = 15), lipid-poor adenomas (n = 13), and metastatic infiltration/infection (n = 9). In the good washout group, pheochromocytomas (n = 15) showed larger diameters (6.00 vs 3.45 cm, P = .001), higher necrosis frequency (73.3% vs 30%, P = .049), and greater arterial attenuation (173.2 vs 74.5 HU, P < .001) compared to adenomas (n = 9). Arterial attenuation provided a high discriminatory value [area under the curve (AUC): 0.967], with 100% sensitivity at 87.6 Hounsfield unit (HU) and 100% specificity at 139.9 HU. In the poor washout group, pheochromocytomas (n = 20) exhibited higher arterial attenuation (99.2 vs 59.2 HU, P < .001; AUC: 0.844) compared to ACC (n = 14), metastatic infiltration (n = 9), and adenomas (n = 4), with 85% sensitivity and 78% specificity at 73.3 HU. Normetanephrine-secreting/nonsecretory pheochromocytomas showed higher arterial enhancement than metanephrine-secreting ones (132.0 vs 90.5 HU, P = .020) within the poor washout group., Conclusion: Arterial phase attenuation on CT has good diagnostic accuracy for differentiating pheochromocytomas from other adrenal masses in both good and poor washout categories, potentially guiding hormonal workup., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Unrelieved cancer pain can seriously reduce patients' quality of life. Hydromorphone based patient-controlled analgesia (PCA) is widely used in surgery. In recent years, it has also gained attention in the field of cancer pain. We report the case of an older patient with refractory pain secondary to colorectal cancer for whom PCA therapy led to improved symptomatic outcomes., Case Description: We present the case of a 79-year-old male with severe pain from advanced colon cancer. After receiving anti-cancer therapy for 7 years, the patient developed pain in the right groin with a pain score of 7/10. The results of whole-body bone imaging suggested the underlying cause to be a pelvic osseous metastasis. Contemporaneous computed tomography (CT) scanning confirmed disease progression in previously noted non-osseous sites of disease. Systemic therapy with bevacizumab, oxaliplatin, and raltitrexed was commenced. For pain palliation, the patient was treated with morphine hydrochloride tablets, morphine hydrochloride injections, compound codeine phosphate and ibuprofen sustained release tablets, incadronate disodium for injection, and oxycodone hydrochloride sustained-release tablets; despite this, his pain remained poorly controlled. The patient was admitted to hospital with a pain score of 8/10. Other symptoms at presentation included fatigue, anorexia, distress and insomnia. A hydromorphone PCA was initiated, which led to a rapid improvement in the patient's pain. The patient died peacefully 17 days later; his family was highly satisfied., Conclusions: Older patients with cancer experience pain in myriad ways. Patients with advanced cancer pain should receive safe, rapid, and effective pain relief. Hydromorphone-based PCA therapies may provide a valuable therapeutic option for individuals with malignant pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-713/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Objective: To describe the genotype-phenotype characteristics of patients with 21-hydroxylase deficiency from western India and ascertain the prevalence of various phenotypes of 21-hydroxylase deficiency., Methods: Patients with 21-hydroxylase deficiency, diagnosed clinically and biochemically, were prospectively enrolled and classified into salt wasting (SW), simple virilizing (SV), and non-classic (NC) phenotypes and were subjected to genetic testing of CYP21A2 by targeted sequencing and multiplex ligation-dependent probe amplification (MLPA)., Results: Eighty (64; 46, XX) probands with 21-hydroxylase deficiency were analyzed. 41 had SW, 34 had SV, and 5 had NC phenotype. Disease-causing mutations were identified in 158/160 alleles. The common mutations were Deletions/Large Gene Conversions (Del/LGC, 25.6%), p.293-13A/C>G (22.5%), and p.Ile173Asn(18.75%). Exon 6 cluster mutations (Ile236Asn, Val237Glu, Met238Lys) and p.Val282Leu were absent. c.-113G>A+p.Pro31Leu (6.87%) and p.Phe405Ser (2.5%) were rare recurrent mutations with a possible founder effect. Two novel variants (Exon 1, p.Leu49Arg, Exon 8, p.Leu362Ter) were identified and were estimated to have low enzyme activity (<2%)., Conclusion: Del/LGC were the most common mutations identified. The c.-113G>A+p.Pro31Leu and p.Phe405Ser were recurrent variants with possible founder effect. This study also reiterates the low prevalence of NC CAH in Indian cohorts.

Background: The data on Leydig cell hypoplasia (LCH) resulting from biallelic Luteinizing hormone/chorionic gonadotropin receptor (LHCGR) inactivating variants is limited to case series., Methods: We aim to describe our patients and perform systematic review of the patients with LHCGR inactivating variants in the literature. Detailed phenotype and genotype data of three patients from our centre and 85 (46,XY: 67; 46,XX: 18) patients from 59 families with LHCGR-inactivating variants from literature were described., Results: Three 46,XY patients (age 6-18 years) from our center, with two reared as females, had two novel variants in LHCGR. Systematic review (including our patients) revealed 72 variants in 88 patients. 46,XY patients (n = 70, 56 raised as females) presented with pubertal delay (n = 41) or atypical genitalia (n = 17). Sinnecker score ≥3 (suggesting antenatal human chorionic gonadotropin (hCG) inaction) was seen in 80% (56/70), and hCG-stimulated testosterone was low (<1.1 ng/mL) in 77.4% (24/31), whereas puberty/postpubertal age, high luteinizing hormone (LH) (97.6%, 41/42) and low (<1.0 ng/mL) basal testosterone (94.9%, 37/39) was observed in most. Follicle stimulating hormone was elevated in 21/51 of these patients. Variants with <10% receptor function were exclusively seen in cohorts with Sinnecker 4/5 (10/15 vs 0/5, P = 0.033). 46,XX patients (n = 18) presented with oligo/amenorrhea and/or anovulatory infertility and had polycystic ovaries (7/9) with median LH of 10 IU/L (1.2-38)., Conclusion: In summary, this study comprehensively characterizes LHCGR variants, revealing genotype-phenotype correlations and informing clinical management of LCH. In 46,XY LCH patients, pubertal LH inaction is uniform with variable severity of antenatal hCG inaction. Few mutant LHCGR have differential actions for LH and hCG.

Burosumab, a monoclonal antibody directed against the fibroblast growth factor 23 (FGF23), has been approved for the treatment of X-linked hypophosphatemia (XLH). We conducted a systematic review to compare the efficacy and safety of burosumab versus conventional therapy (phosphorus and calcitriol) on XLH treatment. After a comprehensive literature search on MEDLINE/PubMed and Embase, we found nine studies for inclusion in the analysis. Risk of bias was assessed, and a random-effects model was used to determine the effect size. Clinical, biochemical, and radiological parameters of disease severity before and after treatment were analyzed and expressed in standardized mean difference (SMD). Burosumab resulted in normalization of phosphate homeostasis with an increase in renal tubular phosphate reabsorption and significant resolution of skeletal lesions (change in Thacher's total rickets severity score SMD: -1.46, 95% confidence interval [CI]: -1.76 to -1.17, p < 0.001, improvement in deformities, and decline in serum alkaline phosphatase levels [SMD: 130.68, 95% CI: 125.26-136.1, p < 0.001)]. Conventional therapy led to similar improvements in all these parameters but to a lower degree. In adults, burosumab normalized phosphorus levels (SMD: 1.23, 95% CI: 0.98-1.47, p < 0.001) with resultant clinical improvement. Burosumab treatment was well tolerated, with only mild treatment-related adverse effects. The present review indicates a potential role for burosumab in improving rickets, deformities, and growth in children with XLH. Given its superior efficacy and safety profile, burosumab could be an effective therapeutic option in children. We suggest further studies comparing burosumab versus conventional therapy in children and adults with XLH.

Context: Data on the overnight 1 mg-dexamethasone suppression test (ONDST) in renal dysfunction are limited., Objective: We aim to determine the normative range of ONDST cortisol across chronic kidney disease (CKD) stages and reasons for its alteration., Methods: Prospectively, 180 CKD (30 each in G2-G5/5D) patients and 30 healthy controls underwent ONDST 8 Am serum cortisol (chemiluminescent immunoassay [CLIA]). In an exploratory cohort, 45 (15 each: G3b/G4, G5/G5D, and healthy controls) individuals' blood biochemistry for basal (8 Am) cortisol and adrenocorticotropin (ACTH), post-ONDST 8 Am dexamethasone, ACTH, cortisol (CLIA and liquid chromatography-tandem mass spectrometry), and 4 Pm cortisol was collected., Results: Post-ONDST cortisol (µg/dL) correlated inversely ( r  = 0.47; P < .005) with estimated glomerular filtration rate (eGFR) (mL/min/1.73 m 2 ), with 95th percentile being 1.2 in controls, 3.0 in G2, 3.2 in G3a, 4.3 in G3b, 4.7 in G4, 5.7 in G5, and 7.1 in G5D. In the exploratory cohort, basal 8 Am cortisol and ACTH, and post-ONDST dexamethasone were similar among controls and CKD subgroups. ONDST ACTH (for evaluating the hypothalamo-pituitary-adrenal axis) was slightly higher in G5/5D vs controls (8.9 vs 6.1 pg/mL), while it was similar in G3b/G4 vs controls. Median 8 Am ONDST cortisol was similar on CLIA and LC-MS/MS in controls and higher on CLIA in G3b/4 (1.7 vs 1.1 µg/dL; P  = .012) and G5/5D (2.4 vs 1.7 µg/dL; P  = .002) than LC-MS/MS. Post-ONDST serum cortisol drop from 8 Am to 4 Pm was significant in controls (0.5-<0.2 µg/dL) and G3b/4 (1.7-1.2 µg/dL), but not in G5/5D (2.4-2.2 µg/dL)., Conclusion: The normative data of ONDST serum cortisol with eGFR-based cutoffs are useful in evaluating Cushing syndrome in CKD. Prolonged cortisol half-life and immunoassay-related assay cross-reaction are likely contributors to higher ONDST cortisol., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: Data regarding rare FPAs from India, a resource limited setting, are limited. We describe a case series of rare FPAs from a single center in western India., Materials and Methods: This was a retrospective case record review of patients diagnosed between January 2010 and July 2022. The diagnosis was based on biochemical(inappropriately elevated serum FSH/LH) and pathologic (positive immunostaining for FSH/LH) features in patients with FGA, and elevated serum thyroid hormones and normal/elevated TSH in patients with TSHomas., Results: We identified 11 patients with a total of six FGAs (median age 43.5 years, five men, one FGA cosecreting TSH, median largest dimension 40 mm, range 33-60 mm) and six TSHomas (median age 34.5 years, four women, two TSHomas cosecreting GH, median largest dimension 42.5 mm, range 13-60 mm). Symptoms of sellar mass effects led to pituitary imaging in most patients with FGA. Patients with TSHomas had symptoms of excess hormone secretion (GH/TSH) or sellar mass effects. The TSHomas that cosecreted GH/FSH were larger than those secreting only TSH. Transsphenoidal resection was the most common first-line therapy but significant residual disease was frequent (3 out of 6 FGAs and 4 out of 5 TSHomas)., Conclusion: This is the first and second case series of FGAs and TSHomas, respectively, from India. In this study, TSHomas presented at younger age, were larger andhad low surgical cure rates.

Objective: To describe the characteristics of gonadotropin-dependent precocious puberty (GDPP) in Indian children., Methods: Clinical profiles of GDPP (n=78, 61 females) and premature thelarche (n=12) from a single center in Western India were retrospectively studied., Results: Pubertal onset was earlier in boys than girls (29 vs 75 months, respec-tively; P=0.008). The basal luteinizing hormone (LH) was ≥0.3 mIU/mL, except 18% of GDPP girls. At 60 minutes after GnRHa-stimulation, all patients (except one girl) had LH ≥5 mIU/mL. The GnRHa-stimulated LH/FSH ratio was ≥0.34 at 60 minutes in girls with GDPP unlike premature thelarche. Only one girl had an allergic reaction to long-acting GnRH agonist. Among GnRH agonist-treated girls (n=24), the predicted final adult height was -1.67±1.5 SDS, whereas the attained final height was -0.25±1.48 SDS., Conclusion: We establish the safety and efficacy of long acting GnRH agonist therapy in Indian children with GDPP. The 60-minute stimulated serum LH/FSH of ≥0.34 differentiated GDPP from premature thelarche.

Background: Patient-centered care for older adults with CKD requires communication about patient's values, goals of care, and treatment preferences. Eliciting this information requires tools that patients understand and that enable effective communication about their care preferences., Methods: Nephrology clinic patients age ≥60 years with stage 4 or 5 nondialysis-dependent CKD selected one of four responses to the question, "If you had a serious illness, what would be important to you?" Condensed versions of the options were, "Live as long as possible;" "Try treatments, but do not suffer;" "Focus on comfort;" or "Unsure." Patients also completed a validated health outcome prioritization tool and an instrument determining the acceptability of end-of-life scenarios. Patient responses to the three tools were compared., Results: Of the 382 participants, 35% ( n =134) selected "Try treatments, but do not suffer;" 33% ( n =126) chose "Focus on comfort;" 20% ( n =75) opted for "Live as long as possible;" and 12% ( n =47) selected "Unsure." Answers were associated with patients' first health outcome priority and acceptability of end-of-life scenarios. One third of patients with a preference to "Focus on comfort" reported that a life on dialysis would not be worth living compared with 5% of those who chose "Live as long as possible" ( P <0.001). About 90% of patients agreed to share their preferences with their providers., Conclusions: Older adults with advanced CKD have diverse treatment preferences and want to share them. A single treatment preference question correlated well with longer, validated health preference tools and may provide a point of entry for discussions about patient's treatment goals., (Copyright © 2019 by the American Society of Nephrology.)

Context: Palliative care interventions have shown promise in improving quality of life and reducing health-care utilization among patients with chronic organ failure., Objectives: To evaluate the effect of a palliative care intervention for adults with end-stage liver disease., Methods: A randomized controlled trial of patients with end-stage liver disease admitted to the hepatology service at a tertiary referral center whose attending hepatologist indicated they would not be surprised if the patient died in the following year on a standardized questionnaire was performed. Control group patients received usual care. Intervention group patients received inpatient specialist palliative care consultations and outpatient phone follow-up by a palliative care nurse. The primary outcome was time until first readmission. Secondary outcomes included days alive outside the hospital, referral to hospice care, death, readmissions, patient quality of life, depression, anxiety, and quality of end-of-life care over 6 months., Results: The trial stopped early because of difficulties in accruing patients. Of 293 eligible patients, only 63 patients were enrolled, 31 in the intervention group and 32 in the control group. This pace of enrollment was only 25% of what the study had planned, and so it was deemed infeasible to complete. Despite stopping early, intervention group patients had a lower hazard of readmission (hazard ratio: 0.36, 95% confidence interval: 0.16-0.83, P = 0.017) and greater odds of having more days alive outside the hospital than control group patients (odds ratio: 3.97, 95% confidence interval: 1.14-13.84, P = 0.030). No other statistically significant differences were observed., Conclusion: Logistical obstacles hindered completion of the trial as originally designed. Nevertheless, a preemptive palliative care intervention resulted in increased time to first readmission and more days alive outside the hospital in the first six months after study entry., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Older adults with advanced CKD have significant pain, other symptoms, and disability. To help ensure that care is consistent with patients' values, nephrology providers should understand their patients' priorities when they make clinical recommendations., Methods: Patients aged ≥60 years with advanced (stage 4 or 5) non-dialysis-dependent CKD receiving care at a CKD clinic completed a validated health outcome prioritization tool to ascertain their health outcome priorities. For each patient, the nephrology provider completed the same health outcome prioritization tool. Patients also answered questions to self-rate their health and completed an end-of-life scenarios instrument. We examined the associations between priorities and self-reported health status and between priorities and acceptance of common end-of-life scenarios, and also measured concordance between patients' priorities and providers' perceptions of priorities., Results: Among 271 patients (median age 71 years), the top health outcome priority was maintaining independence (49%), followed by staying alive (35%), reducing pain (9%), and reducing other symptoms (6%). Nearly half of patients ranked staying alive as their third or fourth priority. There was no relationship between patients' self-rated health status and top priority, but acceptance of some end-of-life scenarios differed significantly between groups with different top priorities. Providers' perceptions about patients' top health outcome priorities were correct only 35% of the time. Patient-provider concordance for any individual health outcome ranking was similarly poor., Conclusions: Nearly half of older adults with advanced CKD ranked maintaining independence as their top heath outcome priority. Almost as many ranked being alive as their last or second-to-last priority. Nephrology providers demonstrated limited knowledge of their patients' priorities., (Copyright © 2018 by the American Society of Nephrology.)

This paper presents a signal modeling-based new methodology of automatic seizure detection in EEG signals. The proposed method consists of three stages. First, a multirate filterbank structure is proposed that is constructed using the basis vectors of discrete cosine transform. The proposed filterbank decomposes EEG signals into its respective brain rhythms: delta, theta, alpha, beta, and gamma. Second, these brain rhythms are statistically modeled with the class of self-similar Gaussian random processes, namely, fractional Brownian motion and fractional Gaussian noises. The statistics of these processes are modeled using a single parameter called the Hurst exponent. In the last stage, the value of Hurst exponent and autoregressive moving average parameters are used as features to design a binary support vector machine classifier to classify pre-ictal, inter-ictal (epileptic with seizure free interval), and ictal (seizure) EEG segments. The performance of the classifier is assessed via extensive analysis on two widely used data set and is observed to provide good accuracy on both the data set. Thus, this paper proposes a novel signal model for EEG data that best captures the attributes of these signals and hence, allows to boost the classification accuracy of seizure and seizure-free epochs.

Background and Objectives: Prognostic uncertainty is one barrier that impedes providers in engaging patients with CKD in shared decision making and advance care planning. The surprise question has been shown to identify patients at increased risk of dying., Design, Setting, Participants, & Measurements: In our prospective observational study, 488 patients ≥60 years of age with CKD stage 4 or 5 were enrolled. Binary surprise question ( i.e. , "Would you be surprised if this patient died in the next 12 months?") responses were recorded, and dialysis planning preferences, presence of advance care planning documentation, and care preceding death were abstracted., Results: The median patient age was 71 (65-77) years old. Providers responded no and yes to the surprise question for 171 (35%) and 317 (65%) patients, respectively. Median follow-up was 1.9 (1.5-2.1) years, during which 18% of patients died (33% of surprise question no, 10% of surprise question yes; P <0.001). In patients with a known RRT preference (58%), 13% of surprise question no participants had a preference for conservative management (versus 2% of yes counterparts; P <0.001). A medical order ( i.e. , physician order for life-sustaining treatment) was documented in 13% of surprise question no patients versus 5% of yes patients ( P =0.004). Among surprise question no decedents, 41% died at home or hospice, 38% used hospice services, and 54% were hospitalized in the month before death. In surprise question yes decedents, 39% died at home or hospice ( P =0.90 versus no), 26% used hospice services ( P =0.50 versus no), and 67% were hospitalized in the month before death ( P =0.40 versus surprise question no)., Conclusions: Nephrologists' prognostic perceptions were associated with modest changes in care, highlighting a critical gap in conservative management discussions, advance care planning, and end of life care among older adults with CKD stages 4 and 5 and high-risk clinical characteristics., Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2017&#95;09&#95;18&#95;CJASNPodcast&#95;17&#95;11.mp3., (Copyright © 2017 by the American Society of Nephrology.)