An international simulated-use study to assess nurses' preferences between two lanreotide syringes for patients with neuroendocrine tumours or acromegaly (PRESTO 3).

PURPOSE: PRESTO 3 evaluated nurses' preference for the Somatuline® Autogel® syringe versus the Lanreotide Pharmathen syringe after injection-pad testing. METHODS: This international simulated-use study included oncology/endocrinology nurses with ≥ 1 years' experience in managing neuroendocrine tumours (NETs) and/or acromegaly. Each nurse tested both syringes twice in a randomised order before completing an electronic survey. The primary objective was to assess overall preference (%, 95% confidence interval [CI]) for the Somatuline Autogel syringe versus the Lanreotide Pharmathen syringe. Secondary objectives included rating syringe performance and ranking the importance of syringe attributes. RESULTS: Ninety-four nurses were enrolled: mean age, 41.0 (SD, 11.5) years. The percentage of nurses stating a preference ("strong" or "slight") for the Somatuline Autogel syringe (86.2% [95% CI 77.5-92.4%]) was significantly higher than 50% (p < 0.0001). Performance rating was significantly higher for the Somatuline Autogel syringe versus Lanreotide Pharmathen syringe for 10 of the 11 attributes tested (p < 0.05). The syringe attributes considered most important when injecting patients in routine clinical practice were "easy to use from preparation to injection" (30.9%) and "comfortable to handle during use from preparation to injection" (16.0%). The attribute most commonly rated as least important was "fast administration from preparation to injection" (26.6%). CONCLUSION: Nurses strongly preferred the user experience of the Somatuline Autogel syringe over the Lanreotide Pharmathen syringe. "Ease of use" and "comfortable to handle" were the most important syringe attributes, and performance rating was significantly higher with Somatuline Autogel versus Lanreotide Pharmathen syringe for all but one attribute.

Drugs called somatostatin analogues (SSAs) can be used to treat patients with neuroendocrine tumours or acromegaly over a prolonged period of time. SSAs are given as injections and act by slowing the production of hormones by the body and in some cases reducing the growth of the tumour. To help to provide the best care possible, it is important that the syringe used for the injection is easy to use and delivers the SSA effectively. Somatuline Autogel is a syringe that can be used to inject an SSA called lanreotide. Previous studies showed that patients and nurses preferred the injection experience when using the Somatuline Autogel syringe compared with a syringe used to inject another SSA called octreotide long-acting release. A new syringe used for lanreotide injections has been developed recently by a company called Pharmathen. In the PRESTO 3 study, we compared the user experience of the Somatuline Autogel syringe and the Lanreotide Pharmathen syringe. We asked 94 nurses from Europe and the US to test both syringes, in a randomised order, using injection pads, and then to answer questions about their overall preference between the two syringes and how well the syringe performed for a set of syringe features. Overall, 86% of nurses preferred the Somatuline Autogel syringe over the Lanreotide Pharmathen syringe. Of the 11 features of the syringe that we assessed, 10 were rated higher for the Somatuline Autogel syringe than the Lanreotide Pharmathen syringe. The syringe features "ease of use" and "comfortable to handle" were considered the most important. The results of the PRESTO 3 study indicated that there is a difference in the user experience between the syringes, particularly for confidence and ease of use, and that it is important to offer syringe choices to nurses who are using SSA injections to treat patients.

Tall stature and gigantism in transition age: clinical and genetic aspects-a literature review and recommendations.

PURPOSE: Tall stature is defined as height greater than the threshold of more than 2 standard deviations above the average population height for age, sex, and ethnicity. Many studies have described the main aspects of this condition during puberty, but an analysis of the characteristics that the physician should consider in the differential diagnosis of gigantism-tall stature secondary to a pituitary tumour-during the transition age (15-25 years) is still lacking. METHODS: A comprehensive search of English-language original articles was conducted in the MEDLINE database (December 2021-March 2022). We selected all studies regarding epidemiology, genetic aspects, and the diagnosis of tall stature and gigantism during the transition age. RESULTS: Generally, referrals for tall stature are not as frequent as expected because most cases are familial and are usually unreported by parents and patients to endocrinologists. For this reason, lacking such experience of tall stature, familiarity with many rarer overgrowth syndromes is essential. In the transition age, it is important but challenging to distinguish adolescents with high constitutional stature from those with gigantism. Pituitary gigantism is a rare disease in the transition age, but its systemic complications are very relevant for future health. Endocrine evaluation is crucial for identifying conditions that require hormonal treatment so that they can be treated early to improve the quality of life and prevent comorbidities of individual patient in this age range. CONCLUSION: The aim of our review is to provide a practical clinical approach to recognise adolescents, potentially affected by gigantism, as early as possible.

Sellar and parasellar lesions in the transition age: a retrospective Italian multi-centre study.

BACKGROUND: Sellar/parasellar lesions have been studied in the adult and paediatric age range, but during the transition age their epidemiology, clinical manifestations, management and treatment outcomes have been poorly investigated. MATERIALS AND METHODS: An Italian multicentre cohort study, in which hospital records of patients with diagnosis of sellar/parasellar lesions during the transition age and young adulthood (15-25 years), were reviewed in terms of prevalence, clinical and hormonal features at diagnosis, and outcomes where available. Both pituitary neuroendocrine tumours (pituitary tumours, Group A) and non-endocrine lesions (Group B) were included. RESULTS: Among Group A (n = 170, 46.5% macroadenomas), the most frequent were prolactin and GH-secreting tumours, with a female predominance. Among Group B (n = 28), germinomas and Rathke cells cysts were the most common. In Group A, the most frequent hormonal deficiency was gonadal dysfunction. Galactorrhoea and amenorrhoea were relatively common in female patients with prolactinomas. Pre-surgical diabetes insipidus was only seen in Group B, in which also hormone deficiencies were more frequent and numerous. Larger lesions were more likely to be seen in Group B. Patients in Group B were more frequently male, younger, and leaner than those of Group A, whereas at last follow-up they showed more obesity and dyslipidaemia. In our cohort, the percentage of patients with at least one pituitary deficiency increased slightly after surgery. CONCLUSIONS: The management of sellar/parasellar lesions is challenging in the transition age, requiring an integrated and multidisciplinary approach. Hormone and metabolic disorders can occur many years after treatment, therefore long-term follow-up is mandatory.

Hearing threshold shifts among military pilots of the Israeli Air Force.

BACKGROUND: Military aviators are potentially at risk for developing noise-induced hearing loss. Whether ambient aircraft noise exposure causes hearing deficit beyond the changes attributed to natural ageing is debated. The aim of this research was to assess changes in hearing thresholds of Israeli Air Force (IAF) pilots over 20 years of military service and identify potential risk factors for hearing loss. METHODS: A retrospective cohort analysis was conducted of pure-tone air conduction audiograms of pilots, from their recruitment at 18 years of age until the last documented medical check-up. Mean hearing thresholds were analysed in relation to age, total flight hours and aircraft platform. Comparisons were made to the hearing thresholds of air traffic controllers (ATCs) who were not exposed to the noise generated by aircraft while on duty. RESULTS: One hundred and sixty-three pilots were included, with flying platforms ranging from fighter jets (n=54), combat helicopters (n=27), transport helicopters (n=52) and transport aircraft (n=30). These were compared with the results from 17 ATCs. A marked notch in the frequency range of 4-6 kHz was demonstrated in the mean audiograms of all platforms pilots, progressing with ageing. Hearing threshold shifts in relation to measurements at recruitment were first noted at the age of 30 years, particularly at 4 kHz (mean shift of 2.97 dB, p=0.001). There was no statistical association between flying variables and hearing thresholds adjusted for age by logistic regression analysis. CONCLUSIONS: The audiometric profile of IAF pilots has a pattern compatible with noise exposure, as reflected by characteristic noise notch. However, no flight variable was associated with deterioration of hearing thresholds, and no significant difference from non-flying controls (ATCs) was seen.

New onset diabetes after kidney transplantation is associated with increased mortality-A retrospective cohort study.

OBJECTIVE: Clinical outcomes in individuals with new onset diabetes after transplantation (NODAT) and the optimal treatment for this complication are poorly characterized. This study was intended to better define these issues. METHODS: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in the study. Clinical outcomes were compared between those who developed NODAT and those who did not. In those who developed NODAT, oral therapy was compared with insulin based therapy. RESULTS: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Using Cox multivariate analysis adjusted for age and gender, hazard ratio for overall mortality among patients with NODAT versus those without NODAT was 2.69 (95% CI 1.04-7.01). Among patients who developed NODAT, 29 patients (40%) were treated with an insulin-based regimen. At the end of follow-up, no difference was found in mean HbA1c, and therapy regimen was not associated with greater mortality. CONCLUSIONS: New onset diabetes in kidney transplanted patients is associated with increased mortality compared with kidney transplanted patients without NODAT.

Are Thyroid Hormone Values Obtained in Hospitalized Elderly Patients Reproducible? - A Cohort Study.

It is unclear whether TSH should be obtained in elderly hospitalized patients as several factors associated with hospitalization influence these levels, which may not truly represent the thyroid status of the individual. All patients≥65 years old hospitalized in a geriatric ward in the years 2012-2014 had TSH measured irrespective of the cause for hospitalization. All patients in whom TSH levels were performed in an ambulatory setting 2-12 months following hospitalization were identified and these TSH levels were correlated with levels recorded during hospitalization. Factors influencing TSH reproducibility were identified through review of patients' medical records. Of 562 patients hospitalized during the study period, 198 had repeat ambulatory TSH measurements during follow-up. The Katz Index of Independence was higher (9.43±2.98 vs. 8.43±3.67 p=0.002) and cerebrovascular disease was less prevalent (15.6 vs. 25.2% p=0.014) in those who had a repeat TSH measurement compared with those who did not, but other baseline characteristics and TSH levels on admission were similar. Ambulatory TSH values were significantly correlated with those obtained during hospitalization (correlation coefficient=0.677), irrespective of baseline systolic blood pressure, cause of hospitalization, or admission albumin levels. Mean TSH difference between in-hospital and ambulatory was 0.65±2.36 mIU/l and in more than 94% of cases TSH values differed by less than 2 mIU/l between the 2 measurements. In hospitalized patients≥65 years old, TSH levels are highly concordant with ambulatory values. TSH obtained during hospitalization may be used for making treatment decisions and has clinical utility in this population.

Blood pressure response to medical treatment in the emergency department - a retrospective cohort study.

OBJECTIVES: It is unclear whether blood pressure (BP) without target organ damage should be decreased in patients in the emergency department (ED). It is also uncertain whether any certain class of medications has an advantage over the other in this setting. This study addressed both these questions. METHODS: In this retrospective cohort study, all patients attending a tertiary care ED with elevated BP were evaluated. All patients with target organ damage as well as those with significant active co-morbidities, such as myocardial ischemia, were excluded. Baseline characteristics and response of BP to therapy were compared between those treated and untreated in the ED. In addition, BP response to therapy was compared between different classes of antihypertensive medications. RESULTS: Overall, 438 patients were included in the final analysis (62% female), of which 275 (63%) were treated in the ED. Antihypertensive medications were more commonly prescribed in the ED for those with higher systolic and diastolic BP, but other baseline characteristics were similar between the two groups. Only systolic BP significantly decreased in those treated with antihypertensive medications compared with those untreated. The most commonly used classes were angiotensin converting enzyme inhibitors (ACEis) and calcium channel blockers (CCBs). Use of either of these drug classes was not associated with a significant decrease in either systolic or diastolic BP compared with the use of other drug classes. CONCLUSIONS: Antihypertensive drug therapy is more commonly prescribed in the ED in individuals with both elevated systolic and diastolic BP, but leads to a significant decrease only in systolic BP. Use of either ACEis or CCBs is not associated with a significant decrease in either systolic or diastolic BP compared with other drug classes.

The management of pre-hypertension in primary care: Is it adequate?

BACKGROUND: Pre-hypertension (pHT) is frequently diagnosed in the primary care setting, but its management by primary care physicians (PCPs) is not well characterized. METHODS: All individuals aged 30-45 years who were insured by Clalit Health services in the Tel Aviv district and had their blood pressure (BP) measured from January 2006 to December 2010 were evaluated. Individuals were divided into three groups based on their initial BP value: optimal (< 120/80 mmHg), normal (systolic BP 120-129 or diastolic 80-84 mmHg) and borderline (130-139/85-89 mmHg). Groups were compared regarding clinical and laboratory follow-up performed by their PCP. RESULTS: Of the 20,214 individuals included in the study, 6576 (32.5%) had values in the pHT range. Of these, 2126 (32.3% of those with pHT) had BP values defined as "borderline" and 4450 (67.6% of those with pHT) had BP values defined as "normal". The number of follow-up visits by the PCP and repeat BP measurement were similar in those with "optimal" BP and pHT. A third and fourth BP measurement were recorded more frequently in those with pHT. In those with pHT, there were more recorded BP measurements than in those with borderline BP (3.35 ± 3 vs. 3.23 ± 2.6), but the time from the initial to the second measurement and a record of a third and fourth measurement were the same in the two groups. CONCLUSION: Identification of pHT does not lead to a significant change in follow-up by PCPs, irrespective of BP values in the pHT range.

A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to COVID-19: a randomised clinical study.

High-dose inhaled Nitric Oxide (iNO) has been shown to have anti-inflammatory, vasodilator, and antimicrobial properties, resulting in improved arterial oxygenation as well as a beneficial therapeutic effect on lower respiratory tract infections. This study evaluated the safety and efficacy of 150-ppm intermittent iNO administered with a novel iNO-generator, for treating adults hospitalised for viral pneumonia. In this prospective, open-label, multicenter study, subjects aged 18-80, diagnosed with viral pneumonia received either standard supportive treatment alone (Control-Group) or combined with iNO for 40 min, 4 times per day up to 7 days (Treatment-Group). Out of 40 recruited subjects, 35 were included in the intention-to-treat population (34 with COVID-19). Adverse Events rate was similar between the groups (56.3% vs. 42.1%; respectively). No treatment-related adverse events were reported, while 2 serious adverse events were accounted for by underlying pre-existing conditions. Among the Treatment-Group, oxygen support duration was reduced by 2.7 days (Hazard Ratio = 2.8; p = 0.0339), a greater number of subjects reached oxygen saturation ≥ 93% within hospitalisation period (Hazard Ratio = 5.4; p = 0.049), and a trend for earlier discharge was demonstrated. Intermittent 150-ppm iNO-treatment is well-tolerated, safe, and beneficial compared to usual care for spontaneously breathing hospitalised adults diagnosed with COVID-19 viral pneumonia.

Sequelae and survivorship in patients treated with (131)I-MIBG therapy.

BACKGROUND: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae. METHODS: Fifty-eight patients with metastatic NETs and CCTs who had received (131)I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated. RESULTS: In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of (131)I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of (131)I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function. CONCLUSION: Long follow up of (131)I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.

The therapy of Cushing's disease in adults and children: an update.

Cushing's disease (CD) is a rare endocrine disorder resulting from excessive production of adrenocorticotrophin hormone by a pituitary adenoma. The consequent hypercortisolaemia gives rise to characteristic features of the disease and its morbidities. Treatments aim to restore normal cortisol levels, provide long-term control of the disease and the tumour, and the improvement of patient well-being. The first line of treatment remains transsphenoidal surgery with remission rates of 65-90% in CD secondary to a pituitary microadenoma. Second-line treatment includes repeat surgery, radiotherapy, medical therapy, and bilateral adrenalectomy. The success rate of radiotherapy ranges from 46% to 74% and is probably independent of the mode of delivery of the radiation, but may take several years to become effective. Medical therapy is useful in acutely unwell patients or while awaiting radiotherapy to become effective. The most often-used medical agents include metyrapone and ketoconazole, which inhibit steroidogenesis; less often, centrally-acting drugs or a glucocorticoid receptor blocker are used, but experience with them is more limited. Bilateral adrenalectomy remains an important treatment option to control unresponsive severe hypercortisolism, particularly in patients with severe CD.The management of childhood CD does not differ from adult disease, with transsphenoidal surgery as successful as in adults but radiotherapy is more rapid in onset. Regardless of the age of the patient, Cushing's disease remains a challenge to the physician and requires a multidisciplinary approach to achieve the most desirable outcome.

Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4.

Inherited causes account for about 50% of individuals presenting with childhood (prelingual) hearing loss, of which 70% are due to mutation in numerous single genes which impair auditory function alone (non-syndromic). The remainder are associated with other developmental anomalies termed syndromic deafness. Genes responsible for syndromic forms of hearing loss include the COL4A5 gene in Alport syndrome and the PAX3 and MITF genes in Waardenburg syndrome. Pendred syndrome is an autosomal recessive disorder associated with developmental abnormalities of the cochlea, sensorineural hearing loss and diffuse thyroid enlargement (goitre). Pendred syndrome is the most common syndromal form of deafness, yet the primary defect remains unknown. We have established a panel of 12 families with two or more affected individuals and used them to search for the location of the Pendred gene by linkage analysis. We excluded localization to four previously mapped nonsyndromic deafness loci but obtained conclusive evidence for linkage of the Pendred syndrome gene to microsatellite markers on chromosome 7q31 (D7S495 Zmax 7.32, Qmax = 0). This region contains a gene, DFNBL, for autosomal recessive non-syndromic sensorineural hearing loss. Multipoint analysis indicates that DFNB4 and Pendred syndrome co-localize to the same 5.5 centiMorgan (cM) interval flanked by D7S501 and D7S523. These data raise the possibility that Pendred syndrome is either allelic with DFNB4 or may represent an inherited contiguous gene disorder, not clinically manifest in the heterozygote.

Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs).

These guidelines update previous guidance published in 2005. They have been revised by a group who are members of the UK and Ireland Neuroendocrine Tumour Society with endorsement from the clinical committees of the British Society of Gastroenterology, the Society for Endocrinology, the Association of Surgeons of Great Britain and Ireland (and its Surgical Specialty Associations), the British Society of Gastrointestinal and Abdominal Radiology and others. The authorship represents leaders of the various groups in the UK and Ireland Neuroendocrine Tumour Society, but a large amount of work has been carried out by other specialists, many of whom attended a guidelines conference in May 2009. We have attempted to represent this work in the acknowledgements section. Over the past few years, there have been advances in the management of neuroendocrine tumours, which have included clearer characterisation, more specific and therapeutically relevant diagnosis, and improved treatments. However, there remain few randomised trials in the field and the disease is uncommon, hence all evidence must be considered weak in comparison with other more common cancers.

The molecular pathogenesis of pituitary tumors: implications for clinical management.

Pituitary adenomas are unique in several ways, and while they are rarely malignant they may be invasive and/or recurrent. Several attempts have been made to determine the growth potential of pituitary adenomas. Pituitary tumors predominantly arise in a sporadic setting or more rarely as part of hereditary genetic syndromes. Molecular analysis of these familial pituitary adenomas has provided significant insight into pituitary tumorigenesis. Some specific genes have been identified that predispose to pituitary neoplasia, but these are rarely involved in the pathogenesis of sporadic tumors. The number of genes or molecular alterations involved in pituitary tumorigenesis is progressively increasing, providing a hope for development of new predictive and prognostic markers. The aim of this review is to focus on the molecular pathology of pituitary adenomas in the context of their implications on management and targeted therapy. We have summarized our current knowledge on the molecular biology in familial and sporadic pituitary adenomas, and we subsequently focus on prognostic factors as well as specific predictive markers for new promising targeted therapies.

The effect of exogenous glucocorticoids on plasma catecholamines and metanephrines in patients without phaeochromocytomas.

The aim of the study was to evaluate the effects of steroid administration under standardised conditions in a range of patients both normal and with adrenal pathologies and to review the impact on plasma catecholamines and metanephrines. Corticosteroid administration has been linked to the development of hypertensive crises in patients with phaeochromocytoma, however a mechanism for this is not fully understood. We aimed to add useful information about the effect of steroids on levels of these hormones under usual circumstances. A prospective, observational cohort study of 50 patients undergoing the low-dose dexamethasone suppression test (LDDST) was undertaken. Additional blood samples were taken at the start and end of the standard LDDST. Biochemical analysis was carried out for plasma catecholamines and plasma free metanephrines. Demographic and hormonal data were acquired from review of the notes or measured at baseline. No significant changes in plasma catecholamines or metanephrines were seen at the end of the LDDST compared to baseline. This was also true of subgroup analysis, divided by age, gender, or type of underlying pathology. Our results suggest that hypertensive reaction responses, rare as they are, are unlikely to be related to normal adrenal physiology. Thus LDDST is likely to be safe under most circumstances, however caution should be exercised in patients with adrenal masses with imaging characteristics compatible with phaeochromocytoma. It may be prudent to defer glucocorticoid administration until functioning phaeochromocytoma has been excluded biochemically.

Interleukin 4 expressed in situ selectively alters thymocyte development.

Using a transgenic mouse model we show that increased intrathymic expression of interleukin 4 (IL-4) significantly perturbs the development of thymocytes. Transgenic double-positive (CD4+CD8+) thymocytes, which are present in dramatically reduced numbers, exhibit increased T cell receptor (TCR) expression and increased mobilization of calcium mediated by these receptors. In contrast, transgenic single-positive (CD4+CD8- and CD4-CD8+) thymocytes and peripheral T cells exhibit decreased TCR-mediated calcium mobilization. The development of CD4-CD8+ thymocytes is significantly perturbed by IL-4 expressed in vivo; only peripheral CD4+ T cells are found in significant numbers in transgenic mice, while CD4-CD8+ thymocytes are present in increased numbers, apparently because of their failure to emigrate to the periphery. In contrast to these selective effects on T cell development, no significant differences in the numbers of B cells or mast cells, or in the plasma levels of IgE and IgG1 are observed between transgenic and control mice. These observations suggest that IL-4 in vivo exerts its major effects locally rather than systemically, even when its expression is constitutively increased.

Renin-angiotensin system inhibitors in management of hypertension during the COVID-19 pandemic.

COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.

Metabolic control of acclimation to nutrient deprivation dependent on polyphosphate synthesis.

Polyphosphate, an energy-rich polymer conserved in all kingdoms of life, is integral to many cellular stress responses, including nutrient deprivation, and yet, the mechanisms that underlie its biological roles are not well understood. In this work, we elucidate the physiological function of this polymer in the acclimation of the model alga Chlamydomonas reinhardtii to nutrient deprivation. Our data reveal that polyphosphate synthesis is vital to control cellular adenosine 5'-triphosphate homeostasis and maintain both respiratory and photosynthetic electron transport upon sulfur deprivation. Using both genetic and pharmacological approaches, we show that electron flow in the energy-generating organelles is essential to induce and sustain acclimation to sulfur deprivation at the transcriptional level. These previously unidentified links among polyphosphate synthesis, photosynthetic and respiratory electron flow, and the acclimation of cells to nutrient deprivation could unveil the mechanism by which polyphosphate helps organisms cope with a myriad of stress conditions in a fluctuating environment.

Treatment of pituitary-dependent Cushing's disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial.

CONTEXT: There is currently no medical therapy for Cushing's disease that targets the pituitary adenoma. Availability of such a medical therapy would be a valuable therapeutic option for the management of this disorder. OBJECTIVE: Our objective was to evaluate the short-term efficacy of the novel multireceptor ligand somatostatin analog pasireotide in patients with de novo, persistent, or recurrent Cushing's disease. DESIGN: We conducted a phase II, proof-of-concept, open-label, single-arm, 15-d multicenter study. PATIENTS: Thirty-nine patients with either de novo Cushing's disease who were candidates for pituitary surgery or with persistent or recurrent Cushing's disease after surgery without having received prior pituitary irradiation. INTERVENTION: Patients self-administered sc pasireotide 600 microg twice daily for 15 d. MAIN OUTCOME MEASURE: Normalization of urinary free cortisol (UFC) levels after 15 d treatment was the main outcome measure. RESULTS: Of the 29 patients in the primary efficacy analysis, 22 (76%) showed a reduction in UFC levels, of whom five (17%) had normal UFC levels (responders), after 15 d of treatment with pasireotide. Serum cortisol levels and plasma ACTH levels were also reduced. Steady-state plasma concentrations of pasireotide were achieved within 5 d of treatment. Responders appeared to have higher pasireotide exposure than nonresponders. CONCLUSIONS: Pasireotide produced a decrease in UFC levels in 76% of patients with Cushing's disease during the treatment period of 15 d, with direct effects on ACTH release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.