Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu.

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH.

Parathyroid Carcinoma Complicated by Parathyromatosis and Refractory Hypercalcemia.

Parathyroid carcinoma (PC) is a rare malignancy. In January 2022, a 41-year-old woman presented with weight loss, proximal muscle weakness, and bone pain. She was diagnosed with severe hypercalcemia with serum calcium of 15.5 mg/dL (8.8-10.6 mg/dL). A biopsy of cervical lymphadenopathy revealed non-caseating granulomatous lymphadenitis. Primary hyperparathyroidism was subsequently confirmed with parathormone (PTH) exceeding 2,500 pg/mL (12-88 pg/mL), leading to left-superior parathyroidectomy and hemithyroidectomy. Histopathology suggested PC versus adenoma, with oxyphilic cells. Postoperatively, she manifested severe hypocalcemia and vitamin D deficiency alongside elevated PTH levels. In January 2023, she experienced a hypercalcemic crisis and developed a new right-sided neck mass. Wide excision revealed PC with parathyromatosis. By September 2023, another hypercalcemic crisis and new left cervical nodules necessitated further surgery, confirming PC deposits in the neck, though without lymph node metastases. Despite treatment with cinacalcet and zoledronic acid, her hypercalcemia persisted until denosumab produced a dramatic response (serum calcium dropping from 16.7 to 7.9 mg/dL; PTH 1,168 pg/mL). However, she remains at risk for progressive local disease and potential distant metastases.

National needs assessment of emergency medicine faculty regarding scholarly activity practices and support.

Objectives: We aimed to assess the attitudes and perceptions of scholarly activity (SA) practices among emergency medicine (EM) physicians who are engaged in training residents. This study examined the belief and need for modern-day SA, potential barriers, and department resources provided. Methods: We conducted a descriptive cross-sectional survey study of EM physicians across the United States identified from the American College of Emergency Physicians and American College of Osteopathic Physicians directories. The survey consisted of 18 items regarding demographics, attitude toward SA, department support, and questions regarding residency programs. Results: A total of 660 survey recipients completed the survey out of a possible pool of 4296 individuals (15% response rate), of which 530 (80%) indicated they were core faculty. Of core faculty, 428 (80.8%) were part of an allopathic program, whereas 102 (19.2%) were part of an osteopathic program. Department support was provided for protected time (385; 58.3%), research staff (346; 52.4%), Institutional Review Board preparation (240; 36.4%), and biostatistics (314; 47.6%). Of all the institutional roles, the largest percentage (82/125, 65.6%) of chair/vice chair/associate chairs strongly agreed or agreed (score of 5 or 4 of 5) with the statement, "Overall, I am satisfied with the scholarly support provided by my department." There was no difference in agreement with this statement between respondents in an allopathic versus osteopathic program (210/428, 49.1% allopathic; 45/102, 44.1% osteopathic). Conclusion: There is a need for increased departmental support for SA. To optimally implement the Accreditation Council for Graduate Medical Education (ACGME) SA requirements into strategy and action, the ACGME should consider providing EM residency programs with an outline of best SA practices to foster a uniform consensus across academic institutions.

Complex Presentation of Pheochromocytoma: Hypertensive Encephalopathy and Takotsubo-Like Cardiomyopathy in a Young Female.

BACKGROUND Pheochromocytoma, a rare catecholamine-secreting tumor, often presents with paroxysmal or sustained hypertension, tachycardia, headache, and diaphoresis. Timely diagnosis is essential to prevent adverse complications. Less common presentations include pheochromocytoma crisis, with severe neurological and cardiac complications. CASE REPORT We report a unique case of a 25-year-old woman who initially presented with pheochromocytoma-induced hypertensive encephalopathy and acute coronary syndrome. Echocardiography revealed takotsubo-like cardiomyopathy, and magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Initial treatment focused on controlling her blood pressure and supporting cardiac function. Due to her recovering from immediate crisis and absence of further symptoms, the patient refused further follow-up. However, she eventually experienced another episode of hypertensive crisis 2 years later. Subsequent investigations with 24-h urine tests revealed elevated vanillylmandelic acid levels (7.93 mg/24 h), normetanephrine (2638.72 µg/24 h), and nor-metanephrine to creatinine ratio (3546.67) and normal urine metanephrine levels (195.92 µg/24 h) and metanephrine to creatinine ratio (263.33). Contrast-enhanced computed tomography of the abdomen revealed a 4.3×3.1×4-cm mass in the right adrenal gland. A DOTATATE positron emission tomography scan revealed a 3.9×4.3×2.7-cm localized right adrenal pheochromocytoma. Biochemical testing and adrenal imaging revealed a previously undiagnosed pheochromocytoma. Following targeted medical therapy and right adrenalectomy, the patient achieved complete resolution of her hypertension and associated symptoms. CONCLUSIONS Our case is a unique simultaneous presentation of posterior reversible encephalopathy syndrome and takotsubo-like cardiomyopathy, highlighting the importance to consider pheochromocytoma in acute neurological and cardiac presentations, even in the absence of typical symptoms.

Understanding social risk factors in patients presenting to the emergency Department for Acute Heart Failure: A pilot study.

BACKGROUND: The standard of care for congestive heart failure (CHF) aims to slow disease progression and maximize patient function, however there is an increase in emergency department (ED) revisits and readmissions. Social risk factors play a role in the disease management and prognosis of CHF. There is a gap in the identification of low-risk CHF patient who would be safely discharged using an initial social risk factor stratification. OBJECTIVES: To generate a social risk profile for patients presenting to the ED with acute CHF exacerbation and identify variables that may increase the risk of 7-day and overall mortality, 30-day ED revisit, and readmission. METHODS: We conducted a pilot prospective survey-based study among adult patients presenting to the ED with acute CHF exacerbation. The combination of a self-report questionnaire and retrospective chart review was used to generate a CHF risk profile. RESULTS: A total of 62 patients were recruited in the pilot study with a mean age of 69.5 years. The preliminary data indicated that prior to this ED visit, 21% of patients were not aware of a previous CHF diagnosis; 64.5% of patients rated their sleep quality as poor or very poor; 72.6% reported orthopnea; and 43.5% reported recent weight gain. 37.1% of patients did not adhere to dietary recommendations and some patients did not adhere to their medication regime 100%. CONCLUSION: This study suggests establishing a social risk profile for patients presenting to the ED with CHF can help formulate a CHF-specific care plan and optimize multidisciplinary management to reduce ED revisits and readmissions.

Low respiratory quotient correlates with high mortality in patients undergoing mechanical ventilation.

OBJECTIVE: Oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), which is the ratio of VO2 to VCO2, are critical indicators of human metabolism. To seek a link between the patient's metabolism and pathophysiology of critical illness, we investigated the correlation of these values with mortality in critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older healthy volunteers and patients who underwent mechanical ventilation were enrolled. A high-fidelity automation device, which accuracy is equivalent to the gold standard Douglas Bag technique, was used to measure VO2, VCO2, and RQ at a wide range of fraction of inspired oxygen (FIO2). RESULTS: We included a total of 21 subjects including 8 post-cardiothoracic surgery patients, 7 intensive care patients, 3 patients from the emergency room, and 3 healthy volunteers. This study included 10 critical care patients, whose metabolic measurements were performed in the ER and ICU, and 6 died. VO2, VCO2, and RQ of survivors were 282 +/- 95 mL/min, 202 +/- 81 mL/min, and 0.70 +/- 0.10, and those of non-survivors were 240 +/- 87 mL/min, 140 +/- 66 mL/min, and 0.57 +/- 0.08 (p = 0.34, p = 0.10, and p < 0.01), respectively. The difference of RQ was statistically significant (p < 0.01) and it remained significant when the subjects with FIO2 < 0.5 were excluded (p < 0.05). CONCLUSIONS: Low RQ correlated with high mortality, which may potentially indicate a decompensation of the oxygen metabolism in critically ill patients.

Efficient Adsorptive Removal of Methylene Blue Dye from Aqueous Solution Using Eragrostis Teff Biomass-Derived Nitrogen and Phosphorus-Codoped Carbon Quantum Dots.

Carbon quantum dots have a great application potential in environmental protection via adsorption technology due to their large specific surface area and negative zeta potential. In this work, nitrogen and phosphorus-codoped carbon quantum dots (NP-CQDs) with a large specific surface area and negative zeta potential were successfully synthesized by a single-step hydrothermal synthesis. Batch adsorption studies were utilized to assess the adsorbent's capacity to remove common methylene blue (MB) dye contaminants from an aqueous solution. The experiment showed that MB dye could be removed in 30 min under optimum experimental conditions, with a removal efficiency of 93.73%. The adsorbent's large surface area of 526.063 m2/g and negative zeta potential of -12.3 mV contribute to the high removal efficiency. The Freundlich isotherm model fits the adsorption process well at 298 K, with R2 and n values of 0.99678 and 4.564, respectively, indicating its applicability. A kinetic study demonstrated that the pseudo-second-order model, rather than the pseudo-first-order model, is more suited to represent the process of MB dye adsorption onto NP-CQDs. This research established a simple and cost-effective method for developing a highly efficient NP-CQD adsorbent for organic dye degradation by adsorption.

Continuous and repeat metabolic measurements compared between post-cardiothoracic surgery and critical care patients.

OBJECTIVE: Using a system, which accuracy is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ), we aimed to continuously measure these metabolic indicators and compare the values between post-cardiothoracic surgery and critical care patients. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Age 18 years or older patients who underwent mechanical ventilation were enrolled. RESULTS: We included 4 post-surgery and 6 critical care patients. Of those, 3 critical care patients died. The longest measurement reached to 12 h and 15 min and 50 cycles of repeat measurements were performed. VO2 of the post-surgery patients were 234 ± 14, 262 ± 27, 212 ± 16, and 192 ± 20 mL/min, and those of critical care patients were 122 ± 20, 189 ± 9, 191 ± 7, 191 ± 24, 212 ± 12, and 135 ± 21 mL/min, respectively. The value of VO2 was more variable in the post-surgery patients and the range of each patient was 44, 126, 71, and 67, respectively. SOFA scores were higher in non-survivors and there were negative correlations of RQ with SOFA. CONCLUSIONS: We developed an accurate system that enables continuous and repeat measurements of VO2, VCO2, and RQ. Critical care patients may have less activity in metabolism represented by less variable values of VO2 and VCO2 over time as compared to those of post-cardiothoracic surgery patients. Additionally, an alteration of these values may mean a systemic distinction of the metabolism of critically ill patients.

Hydrogenation and dehydrogenation of N-heterocycles under Cp*Co(III)-catalysis.

To realize the goal of a carbon-free energy economy, it is crucial to discover reactions that utilize sustainable resources as alternatives to fossil feedstocks. In this study, a well-defined, air-stable Cp*Co(III)-catalyst for transfer hydrogenation of quinoline derivatives and oxidative dehydrogenation of cyclic amines in water is developed. While the former reaction is promoted by formic acid as a transfer hydrogenation reagent, the latter is mediated by molecular oxygen as the sole oxidant. These processes provide new avenues for the investigation of air-stable cobalt catalysts for environmentally benign hydrogenation and dehydrogenation reactions.

Antiviral Drugs and Vaccines for Omicron Variant: A Focused Review.

The Omicron variant of concern (VOC) replaced the delta variant rapidly and became the predominant strain due to more mutations in spike protein and receptor-binding domain (RBD) enhancing its infectivity and binding affinity. The severity of the illness is less than that of the delta variant. Omicron is nonsusceptible to REGEN-COV™ and bamlanivimab with etesevimab. Drugs that are effective against the Omicron variant are oral antiviral drugs such as Paxlovid (nirmatrelvir/ritonavir), remdesivir, sotrovimab, and molnupiravir. The potency of sotrovimab is reduced to 3-fold against Omicron, and 8-fold reduction in potency with sotrovimab is found in a particular variant of Omicron with a R346K substitution in spike protein. There are neither clinical trials comparing the efficacy of these 4 therapies with each other nor any data on a combination of two or more therapies. The current recommendation for mild-moderate, nonhospitalized patients who are at a high risk of disease progression is to use Paxlovid as the first-line option. If Paxlovid is not available or cannot be administered due to drug interactions, then the next best choice is sotrovimab. The third choice is remdesivir if sotrovimab is also not available and molnupiravir is to be given if the other three options are not available or cannot be administered. For prevention, 2130 (cilgavimab) in combination with COV2-2196 (tixagevimab) has been effective against BA.2 only. LY-CoV1404 (bebtelovimab) is recently authorized as it is effective against all sublineages of the Omicron variant. Regarding vaccine efficacy (VE), the 3-dose VE with mRNA vaccines at 14-60 days was found to be 71.6%, and after 60 days, it is 47.4%. There is a 34-38-fold reduction of neutralizing activity with prebooster sera and a 19-fold reduction with booster sera for the Omicron variant. This probably explains the reason for worldwide breakthrough infections with the Omicron variant with waning immunity. The neutralizing antibody response against Omicron elicited by the bivalent vaccine is superior to that of the ancestral Wuhan strain, without any safety concerns. For future advances, the ribosome display technology can be applied for the generation of human single-chain fragment variable (scFv) antibodies from B cells of recovered patients against Omicron and other Coronavirus variants as they are easier and faster to produce and have high affinity and high specificity.

An Automation System Equivalent to the Douglas Bag Technique Enables Continuous and Repeat Metabolic Measurements in Patients Undergoing Mechanical Ventilation.

PURPOSE: To develop a system that is equivalent to the gold standard Douglas Bag (DB) technique for measuring oxygen consumption (V̇o2), carbon dioxide generation (V̇co2), and respiratory quotient (RQ) and to validate its use in clinical settings. METHODS: This was a prospective, observational study conducted at a suburban, quaternary care teaching hospital. Healthy volunteers and patients 18 years or older who received mechanical ventilation were enrolled. FINDINGS: Data from 3 healthy volunteers and 7 patients were analyzed in this study. The interrater reliability between the automation device and DB methods were 0.999, 0.993, and 0.993 for V̇o2, V̇co2, and RQ, respectively. In healthy volunteers, mean (SD) V̇o2, V̇co2, and RQ measured by DB were 411 (100) mL/min, 288 (79) mL/min, and 0.70 (0.03) at high fraction of inspired oxygen (Fio2) and 323 (46) mL/min, 280 (45) mL/min, and 0.85 (0.05) at normal Fio2, respectively. V̇o2 was significantly higher (P < 0.05) and RQ was lower (P < 0.01) in the high Fio2 group as compared to those in the normal Fio2 group. Values measured by the automation system were 227 (31) mL/min, 141 (18) mL/min, and 0.62 (0.04) at high Fio2 and 209 (25) mL/min, 147 (18) mL/min, and 0.70 (0.06) at normal Fio2, respectively. RQ was significantly lower (P < 0.05) in the high Fio2 group as compared to the normal Fio2 group. We also successfully performed continuous and repeat measurements by using the device. The longest measurement reached 12 hours 15 minutes, including 50 cycles of repeat measurements that are equivalent to the DB technique as described above. IMPLICATIONS: We developed an automation system that enables repeat measurements of V̇o2, V̇co2, and RQ, and the accuracy was equivalent to the DB technique. High Fio2 may decrease RQ because of an increase in V̇o2.

Prevalence of chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy in two regions of Australia.

INTRODUCTION/AIMS: Immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) produce significant disability and often require maintenance treatment. There is a paucity of epidemiological data on these conditions in Australia. METHODS: We undertook a prevalence study of CIDP and MMN in North Queensland and Tasmania, coinciding with a national census. Diagnoses were classified against the diagnostic criteria of the European Federation of Neurological Societies/Peripheral Nerve Society. Case ascertainment was undertaken via multiple methods, including survey of local neurologists across public and private clinics, search of neurophysiology, neurology and hospital databases, search of admitted hospital database collections using ICD codes and through immunoglobulin therapy prescription lists. RESULTS: The crude prevalence of CIDP was 5.00 per 100,000 (95% confidence interval [CI] 3.79-6.62) and the crude prevalence of MMN was 1.33 per 100,000 (95% CI 0.78-2.27). Prevalence was also investigated using National Blood Authority numbers of cases prescribed immunoglobulin therapy, indicating a CIDP prevalence of 5.72 per 100,000 (95% CI 4.41-7.43) and MMN prevalence of 1.94 per 100,000 (95% CI 1.24-3.03). There was no significant difference between these numbers and those calculated through access of patient records locally. There was no significant difference in prevalence between Tasmania and North Queensland for any category. DISCUSSION: This study updates the prevalence of CIDP and MMN in Australia. Understanding the distribution of CIDP and MMN patients and their need for treatment is essential for future resource planning and to enable monitoring and coordination of therapies such as immunoglobulin.

Methanol as a hydrogen source: room-temperature highly-selective transfer hydrogenation of α,ß-unsaturated ketones.

The described system offers an ideal, user-friendly protocol for the chemoselective homogeneous hydrogenation of α,ß-unsaturated ketones at room temperature using methanol as a liquid organic hydrogen carrier. Excellent yields were achieved with an in situ-prepared phosphine-free Cp*Ir(III)/bipyridonate complex. Chemoselective reduction with other reducible functionalities and late-stage functionalization were also explored.