Treatment Options in Cushing’s Disease

Endogenous Cushing’s syndrome is a grave disease that requires a multidisciplinary and individualized treatment approach for each patient. Approximately 80% of all patients harbour a corticotroph pituitary adenoma (Cushing’s disease) with excessive secretion of adrenocorticotropin-hormone (ACTH) and, consecutively, cortisol. The goals of treatment include normalization of hormone excess, long-term disease control and the reversal of comorbidities caused by the underlying pathology. The treatment of choice is neurosurgical tumour removal of the pituitary adenoma. Second-line treatments include medical therapy, bilateral adrenalectomy and radiation therapy. Drug treatment modalities target at the hypothalamic/pituitary level, the adrenal gland and at the glucocorticoid receptor level and are commonly used in patients in whom surgery has failed. Bilateral adrenalectomy is the second-line treatment for persistent hypercortisolism that offers immediate control of hypercortisolism. However, this treatment option requires a careful individualized evaluation, since it has the disadvantage of permanent hypoadrenalism which requires lifelong glucocorticoid and mineralocorticoid replacement therapy and bears the risk of developing Nelson’s syndrome. Although there are some very promising medical therapy options it clearly remains a second-line treatment option. However, there are numerous circumstances where medical management of CD is indicated. Medical therapy is frequently used in cases with severe hypercortisolism before surgery in order to control the metabolic effects and help reduce the anestesiological risk. Additionally, it can help to bridge the time gap until radiotherapy takes effect. The aim of this review is to analyze and present current treatment options in Cushing’s disease

Exploiting Low Complexity Beam Allocation in Multi-User Switched Beam Millimeter Wave Systems

Switched-beam systems offer a promising solution for realizing multi-user communications at millimeter wave (mmWave) frequencies. A low-complexity beam allocation (LBA) algorithm has been proposed to solve the challenging problem of maximizing sum data-rates. However, there are practical limitations in mmWave systems, such as restrictions in the number of available radio frequency transceiver chains at the base station, sensitivity to sidelobe interference and the beam generation techniques. In this paper, using generalized beam-patterns, we present the maximum sum data-rates achievable in switched-beam mmWave systems compared with fixed-beam systems by applying LBA. Then, the impact on maximum sum data rates of actual beam-patterns, obtained from a practical mmWave lens antenna, which have higher and non-uniform sidelobes compared with the theoretical beams, is assessed. Finally, as a guide for practical wireless system design, benchmarks are established for relative sidelobe levels that provide acceptable sum data-rate performance when considering generalized beam patterns

Developmental delay in a Streptomyces venezuelae glgE null mutant is associated with the accumulation of alpha-maltose 1-phosphate

The GlgE pathway is thought to be responsible for the conversion of trehalose into a glycogen-like alpha-glucan polymer in bacteria. Trehalose is first converted to maltose, which is phosphorylated by maltose kinase Pep2 to give alpha-maltose 1-phosphate. This is the donor substrate of the maltosyl transferase GlgE that is known to extend alpha-1,4-linked maltooligosaccharides, which are thought to be branched with alpha-1,6 linkages. The genome of Streptomyces venezuelae contains all the genes coding for the GlgE pathway enzymes but none of those of related pathways, including glgC and glgA of the glycogen pathway. This provides an opportunity to study the GlgE pathway in isolation. The genes of the GlgE pathway were upregulated at the onset of sporulation, consistent with the known timing of a-glucan deposition. A constructed Delta glgE null mutant strain was viable but showed a delayed developmental phenotype when grown on maltose, giving less cell mass and delayed sporulation. Pre-spore cells and spores of the mutant were frequently double the length of those of the wild-type, implying impaired cross-wall formation, and spores showed reduced tolerance to stress. The mutant accumulated alpha-maltose 1-phosphate and maltose but no alpha-glucan. Therefore, the GlgE pathway is necessary and sufficient for polymer biosynthesis. Growth of the Delta glgE mutant on galactose and that of a Delta pep2 mutant on maltose were analysed. In both cases, neither accumulation of alpha-maltose 1-phosphate/alpha-glucan nor a developmental delay was observed. Thus, high levels of alpha-maltose 1-phosphate are responsible for the developmental phenotype of the Delta glgE mutant, rather than the lack of a-glucan

Dietary Salt Intake and Mortality in Patients With Type 2 Diabetes

OBJECTIVE: Many guidelines recommend that patients with type 2 diabetes should aim to reduce their intake of salt. However, the precise relationship between dietary salt intake and mortality in patients with type 2 diabetes has not been previously explored. RESEARCH DESIGN AND METHODS: Six hundred and thirty-eight patients attending a single diabetes clinic were followed in a prospective cohort study. Baseline sodium excretion was estimated from 24-h urinary collections (24hU(Na)). The predictors of all-cause and cardiovascular mortality were determined by Cox regression and competing risk modeling, respectively. RESULTS: The mean baseline 24hU(Na) was 184 ± 73 mmol/24 h, which remained consistent throughout the follow-up (intraindividual coefficient of variation [CV] 23 ± 11%). Over a median of 9.9 years, there were 175 deaths, 75 (43%) of which were secondary to cardiovascular events. All-cause mortality was inversely associated with 24hU(Na), after adjusting for other baseline risk factors (P < 0.001). For every 100 mmol rise in 24hU(Na), all-cause mortality was 28% lower (95% CI 6-45%, P = 0.02). After adjusting for the competing risk of noncardiovascular death and other predictors, 24hU(Na) was also significantly associated with cardiovascular mortality (sub-hazard ratio 0.65 [95% CI 0.44-0.95]; P = 0.03). CONCLUSIONS: In patients with type 2 diabetes, lower 24-h urinary sodium excretion was paradoxically associated with increased all-cause and cardiovascular mortality. Interventional studies are necessary to determine if dietary salt has a causative role in determining adverse outcomes in patients with type 2 diabetes and the appropriateness of guidelines advocating salt restriction in this setting

Daratumumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5 ; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse

Massive hemoptysis and deep venous thrombosis presenting in a woman with Hughes-Stovin syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hughes-Stovin syndrome is a very rare disease with fewer than 30 cases reported in the literature. The disease is thought to be a variant of Behcet's disease and is defined by the presence of pulmonary artery aneurysm in association with peripheral venous thrombosis.</p> <p>Case presentation</p> <p>A previously healthy 23-year-old Saudi woman presented with massive hemoptysis a day prior to her admission to our hospital. She had a six-month history of recurrent fever, cough, dyspnea, and recurrent oral ulceration. Contrast-enhanced computed tomography scan of her chest and pulmonary angiogram demonstrated a single right-lower lobe pulmonary artery aneurysm. She underwent thoracotomy and right lower lobe resection. Her postoperative course was complicated by deep vein thrombosis. She also developed headache and papilledema, while a magnetic resonance imaging of her brain suggested vasculitis. Based on these clinical presentations, she was diagnosed and treated with Hughes-Stovin syndrome.</p> <p>Conclusion</p> <p>The majority of cases of Hughes-Stovin syndrome are reported among men, with only two cases occurring in women. A case of Hughes-Stovin syndrome occurring in a woman is presented in this report. She was treated successfully with multimodality treatment that includes surgery, steroids and cytotoxic agents.</p

Public Field Trial of a Multi-RAT (60 GHz 5G/LTE/WiFi) Mobile Network

A public field trial showcasing an operational multi-Radio Access Technology (RAT) mobile network that was implemented in one of the largest shopping mall in Warsaw, Poland. The network supports novel 60 GHz 5G mobile access as well as legacy LTE and WiFi services All mobile access services of the network are interconnected via optical fiber to the data centers of a mobile network operator and an internet service provider. Fronthauling for the 60 GHz 5G hotspot radio access unit (RAU) and for LTE is realized by analog Radio-over-Fiber (RoF) via a fiber-optic distributed antenna system (DAS). The 60 GHz 5G radio access units (RAUs) for the enhanced mobile broadband (eMBB) use case and the WiFi access point (AP) are both backhauled via optical Gigabit Ethernet. The 60 GHz RAUs for the eMBB and hotspot use case feature 2D beam-switching and 1D beam-steering, respectively. Inter-RAT switching between the different mobile services with seamless user experience is achieved using a Mobile IP system with Fast Initial Link Setup (FILS)

Multi RAT (WiFi/ LTE/ 5G) Mobile Network featuring RoF Fronthaul, 60 GHz Beam-Switching and Mobile IP

We report on a public field trial demonstrating seamless handover in a multi Radio Access Technology mobile network supporting WiFi, LTE, and new 5G radio access in the 60 GHz band for full-duplex enhanced mobile broadband and 5G broadcast hotspots

Daratumumab plus lenalidomide and dexamethasone in relapsed/ refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse