Update on clinical characteristics in the evaluation of phaeochromocytoma and paraganglioma.

Pheochromocytomas and sympathetic paragangliomas (PPGL) are rare neuroendocrine tumors originating from chromaffin tissue of the adrenal medulla and extra-adrenal sympathetic paraganglia. Historically, many of these tumors were diagnosed postmortem, earning pheochromocytomas the moniker "great mimic" due to their diverse clinical manifestations that can resemble various other conditions. Over time, the clinical presentation of PPGL has evolved, with a shift from symptomatic or postmortem diagnoses to more frequent incidental discoveries or diagnoses through screening, with postmortem identification now being rare. The development of a clinical scoring system has improved the identification of patients at increased risk for PPGL. Notably, the proportion of PPGL patients with normal blood pressure ranges from 15 % to 40 %, varying based on the clinical context. Despite the tumor's reputation, PPGL is an exceedingly rare cause of resistant hypertension. Management of a pheochromocytoma crisis has advanced, with several classes of drugs available for treatment. However, PPGL during pregnancy remains a significant concern, associated with substantial maternal and fetal mortality rates. Additionally, PPGL can present as rare disorders, including catecholamine-induced cardiomyopathy, Cushing syndrome, and urinary bladder PGL. Given these varied presentations, heightened awareness and prompt recognition of PPGL are crucial for timely diagnosis and treatment, ultimately improving patient outcomes. In this article, we offer an in-depth analysis of the diverse clinical presentations of PPGL, highlighting their complexity and the associated diagnostic and treatment strategies.

Violence study of healthcare workers and systems in the Caribbean: ViSHWaS-Caribbean study.

BACKGROUND: Violence against healthcare workers (HCWs) in the Caribbean continues to prevail yet remains underreported. Our aim is to determine the cause, traits, and consequences of violence on HCWs in the Caribbean. AIM: To determine the cause, traits, and consequences of violence on HCWs in the Caribbean. METHODS: This research adopted an online cross-sectional survey approach, spanning over eight weeks (between June 6th and August 9th, 2022). The survey was generated using Research Electronic Data Capture forms and followed a snowballing strategy to contact individuals using emails, social media, text messages, etc. Logistic regression analysis was performed to evaluate the variables that influence violence, including gender, age, years of experience, institution type, and night shift frequency. RESULTS: The survey was completed by 225 HCWs. Females comprised 61%. Over 51% of respondents belonged to the 21 to 35 age group. Dominica (n = 61), Haiti (n = 50), and Grenada (n = 31) had the most responses. Most HCWs (49%) worked for government academic institutions, followed by community hospitals (23%). Medical students (32%), followed by attending physicians (22%), and others (16%) comprised the most common cadre of respondents. About 39% of the participants reported experiencing violence themselves, and 18% reported violence against colleague(s). Verbal violence (48%), emotional abuse (24%), and physical misconduct (14%) were the most common types of violence. Nearly 63% of respondents identified patients or their relatives as the most frequent aggressors. Univariate logistic regression analyses demonstrated that female gender (OR = 2.08; 95%CI: 1.16-3.76, P = 0.014) and higher frequency of night shifts (OR = 2.22; 95%CI: 1.08-4.58, P = 0.030) were associated with significantly higher odds of experiencing violence. More than 50% of HCWs felt less motivated and had decreased job satisfaction post-violent conduct. CONCLUSION: A large proportion of HCWS in the Caribbean are exposed to violence, yet the phenomenon remains underreported. As a result, HCWs' job satisfaction has diminished.

Healthcare practitioners' experiences in managing HIV among young people in Namibia.

BACKGROUND:  Low viral load suppression rates among older adolescents and young adults with HIV are a global challenge, including in Namibia. Healthcare providers struggle with managing these age groups due to their unique demographic characteristics. Monitoring viral load suppression is vital for evaluating antiretroviral treatment effectiveness, making it essential to identify and address existing gaps. OBJECTIVES:  This study aimed to explore and describe healthcare practitioners' understanding and experiences in managing older adolescents and younger adults living with HIV in seven high-burden districts of Namibia. METHOD:  Qualitative descriptive phenomenological research was followed in this study. Healthcare practitioners directly managing older adolescents and younger adults living with HIV were purposively recruited. Telephonic individual interviews were conducted, and data saturation was achieved with the 29th participant. Colaizzi's seven-step analysis was used to analyse the data. RESULTS:  Two themes emerged from the study: (1) healthcare practitioners' knowledge of viral load management and (2) the strategies employed to manage high viral load in these age groups. These strategies included implementing differentiated service delivery, adopting interprofessional and Ubuntu approaches, psychosocial support, community engagement, enhancing adherence counselling, and support from implementing partners. CONCLUSION:  The findings revealed inadequate knowledge among healthcare practitioners regarding viral load management, which negatively impacts the provision of quality care and an effective HIV response within the spirit of Ubuntu.Contribution: This study enhances healthcare practitioners' capacity in viral load management and guides policy makers in supporting this unique population, thus improving their health outcomes.

Recurrence after surgery for endometrioma: a systematic review and meta-analyses.

IMPORTANCE: Endometriosis is an inflammatory disease, with different forms of expression and a variety of complaints. An endometrioma, an ovarian cyst with endometrium-like lining, is one of the most common expressions of abdominal endometriosis. These endometriomas can, in addition to medical treatment, be treated surgically. After surgery, hormonal therapy is still frequently used for the treatment of endometriosis in general and prevention of recurrence of endometriomas specifically. However, not all women want or can receive postoperative hormonal treatment. It is important for this group to determine the risk of anatomical recurrence of ovarian endometrioma after surgery for an endometrioma. OBJECTIVE: To determine the recurrence rate for surgically treated endometrioma without postoperative hormonal treatment. DATA SOURCES: We performed a systematic literature review and meta-analyses, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. MEDLINE, Embase, and the Cochrane library were searched until May 2023. The literature search was limited to women with endometrioma who received surgical treatment without postoperative hormonal treatment. STUDY SELECTION AND SYNTHESIS: A distinction was made in study design including randomized controlled trials (RCTs) and cohort and retrospective studies. For assessment of risk of bias, the Cochrane Handbook for Systematic Reviews of Interventions and Risk of Bias in Non-randomized Studies - of Interventions assessment tool were used. MAIN OUTCOMES: The outcome measure included in this review was endometrioma recurrence. RESULTS: We screened 5,367 articles, of which 97 were systematically reviewed and 55 were included in this systematic review. Twelve of these were RCTs, 11 were prospective cohort studies, and 32 were retrospective studies. Nine RCTs had a low risk of bias. For non-RCTs, only 3 studies had a low risk of bias. Data of 23 studies were pooled in meta-analyses, performed for follow-up periods of 3, 6, 12, and 24 months. These studies showed recurrence rates of 4%, 14%, 17%, and 27%, respectively. CONCLUSION AND RELEVANCE: In the meta-analysis, at 24 months after surgery, the endometrioma recurrence rate showed a weighted mean of up to 27%. In this study, we aimed to determine the recurrence rate of endometrioma after surgical treatment in women without postoperative hormonal treatment use. The recurrence rates were up to 27%.

International consensus statement on the diagnosis and management of phaeochromocytoma and paraganglioma in children and adolescents.

Phaeochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumours that arise not only in adulthood but also in childhood and adolescence. Up to 70-80% of childhood PPGL are hereditary, accounting for a higher incidence of metastatic and/or multifocal PPGL in paediatric patients than in adult patients. Key differences in the tumour biology and management, together with rare disease incidence and therapeutic challenges in paediatric compared with adult patients, mandate close expert cross-disciplinary teamwork. Teams should ideally include adult and paediatric endocrinologists, oncologists, cardiologists, surgeons, geneticists, pathologists, radiologists, clinical psychologists and nuclear medicine physicians. Provision of an international Consensus Statement should improve care and outcomes for children and adolescents with these tumours.

Same-day discharge after laparoscopic hysterectomy for benign/premalignant disease: A multicentre randomised controlled trial.

OBJECTIVE: To evaluate whether physical function and quality of life was influenced by discharge on the same-day after a total laparoscopic hysterectomy. DESIGN: Multicentre non-inferiority randomised controlled trial. SETTING: Five teaching hospitals and two university hospitals in the Netherlands. POPULATION: Patients undergoing laparoscopic hysterectomy for benign or premalignant disease. METHODS: Following informed consent, participants were allocated 1:1 either to same-day discharge (SDD) or next-day discharge (NDD). MAIN OUTCOME MEASURES: The primary outcome was physical function at 7 days after surgery measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function short Form 10A. Secondary outcomes were physical function and quality of life at 1 and 3 days and 6 weeks after surgery measured with PROMIS short Form 10A and the EuroQol questionnaire (EQ-5D-5L). RESULTS: Two hundred and five patients were included of whom 105 were allocated to SDD and 100 to NDD. Physical function 7 days after surgery was 35.95 in the SDD group and 35.63 in the control group (mean difference 0.32; 95% CI [0.07-0.57]). As the upper limit of the 95% CI does not exceed the non-inferiority margin of 4 points, non-inferiority of SDD could be demonstrated. No difference in physical function nor quality of life on Days 1 and 3 and 6 weeks could be found. CONCLUSION: This research demonstrates same-day discharge after laparoscopic hysterectomy is non-inferior to next day discharge in physical function 7 days after surgery.

Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs.

BACKGROUND: Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR). METHODS: This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate). Receiver operating characteristic curves for steroid-probability scores and the ARR were examined with and without interfering medications. Impacts of individual medications on plasma aldosterone, 18-oxocortisol, 18-hydroxycortisol, steroid-probability scores, renin, and ARRs were examined by multivariable and paired analyses in patients with and without PA. RESULTS: Receiver operating characteristic curves indicated a significant impact of interfering antihypertensive medications on the diagnostic performance of the ARR and minimal impact on steroid-probability scores. Mineralocorticoid receptor antagonists increased plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol in patients without PA and resulted in false-positive test results for steroid-probability scores and false-negative results for the ARR. Diuretics increased aldosterone, 18-oxocortisol, and steroid-probability scores in patients without PA, whereas angiotensin-converting enzyme inhibitors decreased aldosterone, steroid-probability scores, and ARRs. Beta-adrenoceptor blockers, dihydropyridine calcium channel blockers, and angiotensin receptor blockers had negligible impact on mineralocorticoids and steroid-probability scores. CONCLUSIONS: Among antihypertensive drugs that impact plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol, mineralocorticoid receptor antagonists stood out as a cause of false-positive results for derived steroid-probability scores. Other antihypertensives have minimal or no impact, an advantage for use of steroid-probability scores over the ARR when those medications cannot be withdrawn. REGISTRATION: URL: https://drks.de/search/en/trial/DRKS00017084; Unique identifier: DRKS00017084.

A gluten-free diet for endometriosis patients lacks evidence to recommend it.

Endometriosis is an estrogen-dependent chronic disease characterized by the presence of endometriumlike tissue outside the uterus and is often associated with symptoms, such as dysmenorrhea, dysuria, dyschezia, chronic pelvic pain, and infertility. Moreover, women diagnosed with endometriosis can report gastrointestinal symptoms, including bloating, constipation or diarrhea, and abdominal cramping, which can be associated with irritable bowel syndrome and can result in the misdiagnosis of endometriosis as irritable bowel syndrome at first. Treatment usually involves hormonal therapy, pain management, surgery, and/or assisted reproductive techniques in case of infertility. Nonetheless, these treatment methods can be insufficient for alleviating symptoms or can have unacceptable side effects, leading to noncompliance. Therefore, women often apply self-management strategies, including dietary interventions. One of the diets frequently suggested as a tool to manage endometriosis-related symptoms on social media and patient forums is a gluten-free diet. Although a gluten-free diet has been proven effective in managing nonceliac wheat sensitivity or celiac disease, its effectiveness in endometriosis remains uncertain. The Nurses' Health Study II found it unlikely that gluten intake was a strong factor in endometriosis etiology and symptomatology. To the best of our knowledge, the most frequently cited and sole published intervention study on the efficacy of a gluten-free diet for endometriosis has several important limiting factors, including the absence of a control group. In addition, gluten consumption is highly susceptible to a placebo effect and a nocebo effect, where women might experience symptom relief after eliminating gluten and return of symptoms after they consume gluten again, solely because they believe that gluten is bad for them. Despite the inverse association between body mass index and endometriosis and between a gluten-free diet and increased body mass index, this is an association, and no causality was proven. In addition, other factors should be taken into consideration. Of note, a gluten-free diet is expensive, has limited availability, and has a significant effect on quality of life. Moreover, without proper dietary guidance, it may adversely affect the gastrointestinal microbiome. Therefore, scientifically substantiated advice regarding the use of a gluten-free diet for endometriosis-related symptoms is currently not available, and a gluten-free diet should be discouraged unless there is an additional diagnosis of nonceliac wheat sensitivity or celiac disease.

COVID-19 Vaccination Coverage, and Rates of SARS-CoV-2 Infection and COVID-19-Associated Hospitalization Among Residents in Nursing Homes - National Healthcare Safety Network, United States, October 2023-February 2024.

Nursing home residents are at increased risk for developing severe COVID-19. Nursing homes report weekly facility-level data on SARS-CoV-2 infections, COVID-19-associated hospitalizations, and COVID-19 vaccination coverage among residents to CDC's National Healthcare Safety Network. This analysis describes rates of incident SARS-CoV-2 infection, rates of incident COVID-19-associated hospitalization, and COVID-19 vaccination coverage during October 16, 2023-February 11, 2024. Weekly rates of SARS-CoV-2 infection ranged from 61.4 to 133.8 per 10,000 nursing home residents. The weekly percentage of facilities reporting one or more incident SARS-CoV-2 infections ranged from 14.9% to 26.1%. Weekly rates of COVID-19-associated hospitalization ranged from 3.8 to 7.1 per 10,000 residents, and the weekly percentage of facilities reporting one or more COVID-19-associated hospitalizations ranged from 2.6% to 4.7%. By February 11, 2024, 40.5% of nursing home residents had received a dose of the updated 2023-2024 COVID-19 vaccine that was first recommended in September 2023. Although the peak rate of SARS-CoV-2 infection among nursing home residents was lower during the 2023-24 respiratory virus season than during the three previous respiratory virus seasons, nursing home residents continued to be disproportionately affected by SARS-CoV-2 infection and related severe outcomes. Vaccination coverage remains suboptimal in this population. Ongoing surveillance for SARS-CoV-2 infections and COVID-19-associated hospitalizations in this population is necessary to develop and evaluate evidence-based interventions for protecting nursing home residents.

The (cost-) effectiveness Of Surgical excision of Colorectal endometriosis compared to ART treatment trAjectory (TOSCA study) - a study protocol.

Currently, the optimal treatment to increase the chance of pregnancy and live birth in patients with colorectal endometriosis and subfertility is unknown. Evidence suggests that that both surgery and in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are effective in improving live birth rate (LBR) among these women. However, the available evidence is of low quality, reports highly heterogeneous results, lacks direct comparison between both treatment options and does not assess whether a combination strategy results in a higher LBR compared to IVF/ICSI-only treatment. Additionally, the optimal timing of surgery within the treatment trajectory remains unclear. The primary objective of the TOSCA study is to assess the effectiveness of surgical treatment (potentially combined with IVF/ICSI) compared to IVF/ICSI-only treatment to increase the chance of an ongoing pregnancy resulting in a live birth in patients with colorectal endometriosis and subfertility, measured by cumulative LBR. Secondary objectives are to assess and compare quality of life and cost-effectiveness in both groups. Patients will be followed for 40 months after inclusion or until live birth. The TOSCA study is expected to be completed in 6 years.

Patient-reported burden associated with pheochromocytoma/paraganglioma diagnosis.

Pheochromocytoma and paragangliomas (PPGLs) originate from the chromaffin cells of the adrenal medulla or neural crest progenitors outside the adrenal gland, respectively. The estimated annual incidence of PPGL is between 2.0 and 8.0/million adults. Minimal data exist on the impact of PPGL from the patient's perspective. Therefore, a survey was adapted from a previously published study on gastroenteropancreatic neuroendocrine tumors to explore the voice of patients with PPGL and learn ways to improve clinical care while understanding the current gaps to direct future research. A self-reported online survey was available to patients with PPGL and those with genetic predisposition even without PPGL from June to July 2022. Survey questions captured sociodemographic and clinical characteristics, the diagnostic workup, treatment and monitoring, quality and access to care, and financial impact. Here, we report the most relevant findings on patient experience of disease burden following diagnosis. A total of 270 people responded, the majority of whom were from the USA (79%), Caucasian (88%), and female (81%). The results of this survey highlight the burden of disease on a patient's daily life, resulting in moderate to severe financial distress, increased travel time to specialized facilities resulting in loss of work and wages, and significant delays in care. Respondents reported being unheard and unacknowledged. With a median time to diagnosis just over 2 years, the physical, mental, and emotional toll are substantial. Increasing access to PPGL specialists and centers could lead to faster diagnoses and better management, which may reduce the burden on both patients and healthcare centers.

Diagnosis and management of urinary bladder paragangliomas: A Sino-American-European retrospective observational study.

OBJECTIVE: Paragangliomas of the urinary bladder (UBPGLs) are rare neuroendocrine tumours and pose a diagnostic and surgical challenge. It remains unclear what factors contribute to a timely presurgical diagnosis. The purpose of this study is to identify factors contributing to missing the diagnosis of UBPGLs before surgery. DESIGN, PATIENTS AND MEASUREMENTS: A total of 73 patients from 11 centres in China, and 51 patients from 6 centres in Europe and 1 center in the United States were included. Clinical, surgical and genetic data were collected and compared in patients diagnosed before versus after surgery. Logistic regression analysis was used to identify clinical factors associated with initiation of presurgical biochemical testing. RESULTS: Among all patients, only 47.6% were diagnosed before surgery. These patients were younger (34.0 vs. 54.0 years, p < .001), had larger tumours (2.9 vs. 1.8 cm, p < .001), and more had a SDHB pathogenic variant (54.7% vs. 11.9%, p < .001) than those diagnosed after surgery. Patients with presurgical diagnosis presented with more micturition spells (39.7% vs. 15.9%, p = .003), hypertension (50.0% vs. 31.7%, p = .041) and catecholamine-related symptoms (37.9% vs. 17.5%, p = .012). Multivariable logistic analysis revealed that presence of younger age (<35 years, odds ratio [OR] = 6.47, p = .013), micturition spells (OR = 6.79, p = .007), hypertension (OR = 3.98, p = .011), and sweating (OR = 41.72, p = .013) increased the probability of initiating presurgical biochemical testing. CONCLUSIONS: Most patients with UBPGL are diagnosed after surgery. Young age, hypertension, micturition spells and sweating are clues in assisting to initiate early biochemical testing and thus may establish a timely presurgical diagnosis.

Rubisco is evolving for improved catalytic efficiency and CO2 assimilation in plants.

Rubisco is the primary entry point for carbon into the biosphere. However, rubisco is widely regarded as inefficient leading many to question whether the enzyme can adapt to become a better catalyst. Through a phylogenetic investigation of the molecular and kinetic evolution of Form I rubisco we uncover the evolutionary trajectory of rubisco kinetic evolution in angiosperms. We show that rbcL is among the 1% of slowest-evolving genes and enzymes on Earth, accumulating one nucleotide substitution every 0.9 My and one amino acid mutation every 7.2 My. Despite this, rubisco catalysis has been continually evolving toward improved CO2/O2 specificity, carboxylase turnover, and carboxylation efficiency. Consistent with this kinetic adaptation, increased rubisco evolution has led to a concomitant improvement in leaf-level CO2 assimilation. Thus, rubisco has been slowly but continually evolving toward improved catalytic efficiency and CO2 assimilation in plants.

Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study.

BACKGROUND: Measurements of aldosterone by mass spectrometry are more accurate and less prone to interferences than immunoassay measurements, and may produce a more accurate aldosterone:renin ratio (ARR) when screening for primary aldosteronism (PA). METHODS: Differences in diagnostic performance of the ARR using mass spectrometry vs immunoassay measurements of aldosterone were examined in 710 patients screened for PA. PA was confirmed in 153 patients and excluded in 451 others. Disease classifications were not achieved in 106 patients. Areas under receiver-operating characteristic curves (AUROC) and other measures were used to compare diagnostic performance. RESULTS: Mass spectrometry-based measurements yielded lower plasma aldosterone concentrations than immunoassay measurements. For the ARR based on immunoassay measurements of aldosterone, AUROCs were slightly lower (P = 0.018) than those using mass spectrometry measurements (0.895 vs 0.906). The cutoff for the ARR to reach a sensitivity of 95% was 30 and 21.5 pmol/mU by respective immunoassay and mass spectrometry-based measurements, which corresponded to specificities of 57% for both. With data restricted to patients with unilateral PA, diagnostic sensitivities of 94% with specificities >81% could be achieved at cutoffs of 68 and 52 pmol/mU for respective immunoassay and mass spectrometry measurements. CONCLUSIONS: Mass spectrometry-based measurements of aldosterone for the ARR provide no clear diagnostic advantage over immunoassay-based measurements. Both approaches offer limited diagnostic accuracy for the ARR as a screening test. One solution is to employ the higher cutoffs to triage patients likely to have unilateral PA for further tests and possible adrenalectomy, while using the lower cutoffs to identify others for targeted medical therapy.German Clinical Trials Register ID: DRKS00017084.

Imaging of Pheochromocytomas and Paragangliomas.

Pheochromocytomas/paragangliomas are unique in their highly variable molecular landscape driven by genetic alterations, either germline or somatic. These mutations translate into different clusters with distinct tumor locations, biochemical/metabolomic features, tumor cell characteristics (eg, receptors, transporters), and disease course. Such tumor heterogeneity calls for different imaging strategies in order to provide proper diagnosis and follow-up. This also warrants selection of the most appropriate and locally available imaging modalities tailored to an individual patient based on consideration of many relevant factors including age, (anticipated) tumor location(s), size, and multifocality, underlying genotype, biochemical phenotype, chance of metastases, as well as the patient's personal preference and treatment goals. Anatomical imaging using computed tomography and magnetic resonance imaging and functional imaging using positron emission tomography and single photon emission computed tomography are currently a cornerstone in the evaluation of patients with pheochromocytomas/paragangliomas. In modern nuclear medicine practice, a multitude of radionuclides with relevance to diagnostic work-up and treatment planning (theranostics) is available, including radiolabeled metaiodobenzylguanidine, fluorodeoxyglucose, fluorodihydroxyphenylalanine, and somatostatin analogues. This review amalgamates up-to-date imaging guidelines, expert opinions, and recent discoveries. Based on the rich toolbox for anatomical and functional imaging that is currently available, we aim to define a customized approach in patients with (suspected) pheochromocytomas/paragangliomas from a practical clinical perspective. We provide imaging algorithms for different starting points for initial diagnostic work-up and course of the disease, including adrenal incidentaloma, established biochemical diagnosis, postsurgical follow-up, tumor screening in pathogenic variant carriers, staging and restaging of metastatic disease, theranostics, and response monitoring.

Degradation during Mixing of Silica-Reinforced Natural Rubber Compounds.

The optimal mixing conditions for silica-filled NR compounds dictate the need to proceed at a high temperature, i.e., 150 °C, to achieve a sufficient degree of silanization. On the other hand, natural rubber is prone to degradation due to mechanical shear and thermal effects during mixing, particularly at long exposure times. The present work investigates NR rubber degradation during mixing in relation to prolonged silanization times. The Mooney viscosity and stress relaxation rates, bound rubber content, storage modulus (G'), and delta δ were investigated to indicate the changes in the elastic/viscous responses of NR molecules related to rubber degradation, molecular chain modifications, and premature crosslinking/interaction. In Gum NR (unfilled), an increase in the viscous response with increasing mixing times indicates a major chain scission that causes a decreased molecular weight and risen chain mobility. For silica-filled NR, an initial decrease in the Mooney viscosity with increasing silanization time is attributed to the chain scission first, but thereafter the effect of the degradation is counterbalanced by a sufficient silanization/coupling reaction which leads to leveling off of the viscous response. Finally, the higher viscous response due to degradation leads to the deterioration of the mechanical properties and rolling resistance performance of tire treads made from such silica-filled NR, particularly when the silanization time exceeds 495 s.

Plasma Metanephrines Yield Fewer False-Positive Results Than Urine Metanephrines in Patients With Obstructive Sleep Apnea.

CONTEXT: Obstructive sleep apnea (OSA) is associated with increased nocturnal sympathetic activity. In OSA patients, elevations in metanephrines may lead to false-positive tests when evaluating for pheochromocytoma or paraganglioma (PPGL). OBJECTIVE: To evaluate whether morning plasma metanephrines would lead to fewer false-positive results than 24-hour urinary metanephrines in OSA patients. METHODS: Patients undergoing polysomnography for suspected OSA were recruited. Plasma free and 24-hour urinary metanephrines were measured by HPLC-MS/MS. Patients with elevated levels had repeat measurements, abdominal imaging, and follow-up to diagnose or exclude a PPGL. RESULTS: Seventy-six patients completed polysomnography and biochemical testing; 68 (89.5%) patients had OSA, of whom 19 (27.9%) had elevated plasma and/or urinary metanephrines. On follow-up, one patient had a bladder paraganglioma, while PPGL was excluded in the remaining patients. OSA patients had more false-positive urinary metanephrines (17 of 67, 25.4%) than plasma metanephrines (2 of 67, 3.0%), P < .01, and this was more common in severe OSA (13 of 34, 38.2%), compared to moderate/mild OSA (4 of 33, 12.1%), P < .01. Both plasma and urinary metanephrines decreased after treatment with continuous positive airway pressure. On multivariable analysis, severe OSA, obesity, and family history of hypertension were positive predictors for false-positive urinary metanephrines in patients with suspected OSA. CONCLUSION: In OSA patients, plasma metanephrines are less likely to yield false-positive results for the diagnosis of PPGL than 24-hour urinary metanephrines. In patients with suspected OSA, obesity, or a family history of hypertension, plasma metanephrines may be the preferred first-line test to avoid unnecessary anxiety or follow-up.

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.

Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.

Evolution: Unearthing missing links in the origin of our planet's primary carbon-fixing enzyme.

Form I rubisco underpins life on Earth, but the origins of its anomalous and highly complex multimeric structure have long proven elusive. New research helps to unravel this enigma by uncovering key missing links in the enzyme's evolutionary history.