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With the ongoing dramatic growth of radiopharmaceutical therapy, research and development in internal radiation dosimetry continue to advance both at academic medical centers and in industry. The basic paradigm for patient-specific dosimetry includes administration of a pretreatment tracer activity of the therapeutic radiopharmaceutical; measurement of its time-dependent biodistribution; definition of the pertinent anatomy; integration of the measured time-activity data to derive source-region time-integrated activities; calculation of the tumor, organ-at-risk, and/or whole-body absorbed doses; and prescription of the therapeutic administered activity. This paper provides an overview of the state of the art of patient-specific dosimetry for radiopharmaceutical therapy, including current methods and commercially available software and other resources.In this work, we present details and initial results from a 177Lu dosimetry challenge that has been designed to collect data from the global nuclear medicine community aiming at identifying, understanding, and quantitatively characterizing the consequences of the various sources of variability in dosimetry. Methods The challenge covers different approaches to performing dosimetry planar, hybrid, and pure SPECT. It consists of 5 different and independent tasks to measure the variability of each step in the dosimetry workflow. Each task involves the calculation of absorbed doses to organs and tumors and was meant to be performed in sequential order. The order of the tasks is such that results from a previous one would not affect subsequent ones. Different sources of variability are removed as the participants advance through the challenge by giving them the data required to begin the calculations at different steps of the dosimetry workflow. Data from 2 patients after a therapeutic administration of 177Lu-DOTATresults provide insights into the variability associated with performing dose calculations. It is expected that this dataset, including results from future stages, will result in efforts to standardize and harmonize methods and procedures.Radiopharmaceutical therapy (RPT) is defined as the delivery of radioactive atoms to tumor-associated targets. In RPT, imaging is built into the mode of treatment since the radionuclides used in RPT often emit photons or can be imaged using a surrogate. Such imaging may be used to estimate tumor-absorbed dose. We examine and try to elucidate those factors that impact the absorbed dose-versus-response relationship for RPT agents. These include the role of inflammation- or immune-mediated effects, the significance of theranostic imaging, radiobiology, differences in dosimetry methods, pharmacokinetic differences across patients, and the impact of tumor hypoxia on response to RPT.

Increased mortality has been reported in people with insomnia and in those with obstructive sleep apnoea (OSA). However, these conditions commonly co-occur and the combined effect of co-morbid insomnia and sleep apnoea (COMISA) on mortality risk is unknown. This study used Sleep Heart Health Study (SHHS) data to assess associations between COMISA and all-cause mortality risk.

Insomnia was defined as difficulties falling asleep, maintaining sleep, and/or early morning awakenings from sleep ≥16 times a month and daytime impairment. OSA was defined as an apnoea-hypopnoea index ≥15 events/h sleep. COMISA was defined if both conditions were present. Multivariable adjusted Cox proportional hazard models were used to determine the association between COMISA and all-cause mortality (n=1210) over 15 years of follow-up.

5236 participants were included. 2708 (52%) did not have insomnia/OSA (control), 170 (3%) had insomnia-alone, 2221 (42%) had OSA-alone, and 137 (3%) had COMISA. COMISA participants had a higher prevalence of hypertension (ORs [95%CI]; 2.00 [1.39, 2.90]) and cardiovascular disease compared to controls (1.70 [1.11, 2.61]). Insomnia-alone and OSA-alone were associated with higher risk of hypertension but not cardiovascular disease compared to controls. Compared to controls, COMISA was associated with a 47% (HR, 95% CI; 1.47 (1.06, 2.07)) increased risk of mortality. The association between COMISA and mortality was consistent across multiple definitions of OSA and insomnia.

Co-morbid insomnia and sleep apnoea was associated with higher rates of hypertension and cardiovascular disease at baseline, and an increased risk of all-cause mortality compared to no insomnia/OSA.

Co-morbid insomnia and sleep apnoea was associated with higher rates of hypertension and cardiovascular disease at baseline, and an increased risk of all-cause mortality compared to no insomnia/OSA.Mutations in bone morphogenetic protein type II receptor (BMPR2) have been found in patients with congenital heart disease-associated pulmonary arterial hypertension (CHD-PAH). Our study aimed to clarify whether deficient BMPR2 signalling acts through downstream effectors, inhibitors of DNA-binding proteins (IDs), during heart development to contribute to the progress of PAH in CHD patients. To confirm that IDs are downstream effectors of BMPR2 signalling in cardiac mesoderm progenitors (CMPs) and contribute to PAH, we generated Cardiomyocytes (CMs)-specific Id 1/3 knockout mice (Ids cDKO), and 12/25 developed mild PAH with altered haemodynamic indices and pulmonary vascular remodelling. Moreover, we generated ID1 and ID3 double-knockout (IDs KO) human embryonic stem cells that recapitulated the BMPR2 signalling deficiency of CHD-PAH iPSCs. CMs differentiated from induced pluripotent stem cells (iPSCs) derived from CHD-PAH patients with BMPR mutations exhibited dysfunctional cardiac differentiation and reduced Ca2+ transients, as evidenced by confocal microscopy experiments. Smad1/5 phosphorylation and ID1 and ID3 expression were reduced in CHD-PAH iPSCs and in Bmpr2 +/- rat right ventricles. Moreover, Ultrasound revealed that 33% of Ids cDKO mice had detectable defects in their ventricular septum and pulmonary regurgitation. CMs isolated from the mouse right ventricles also showed reduced Ca2+ transients and shortened sarcomeres. Single-cell RNA(scRNA)-seq analysis revealed impaired differentiation of CMPs and downregulated USP9X expression in IDs KO cells compared with wild-type (WT) cells. We found that BMPR2 signals through IDs and USP9X to regulate cardiac differentiation, and the loss of ID1 and ID3 expression contributes to CM dysfunction in CHD-PAH patients with BMPR2 mutations.Long-acting reversible contraceptives (ie, intrauterine devices and the etonogestrel subdermal implant) have become increasingly popular methods of contraception because of their convenience and safety profile. At the same time, the use of depot medroxyprogesterone acetate, one of the most prescribed contraceptives in the United States since its approval in 1992, is on the wane. The history and pros and cons of these contraceptive methods are reviewed.Chronic venous outflow obstruction is a significant cause of chronic venous disease and therefore chronic morbidity. When conservative measures fail, intervention through deep venous reconstructive techniques should be considered. Referral should be considered in all patients with features of chronic venous disease that are life-affecting. Imaging relies primarily on duplex ultrasonography, supplemented by computed tomographic and magnetic resonance venography, and intraoperatively by intravascular ultrasonography. Intervention is primary endovenous, using angioplasty and stenting. Open surgical procedures are used in very select patients.Any survivor among the millions of patients admitted to the intensive care unit (ICU) for critical illness each year is susceptible to persistent health problems that continue after discharge and may lead to post-intensive care syndrome (PICS), defined as new or worsening dysfunction from physical impairment, cognitive impairment, or emotional impairment, or a combination. Considering the increased rates of ICU survival and the growing elderly population more likely to utilize ICU resources, critical care practitioners have broadened their focus on outcomes and care of ICU survivors to include the acute post-ICU survival period as well as months and even years after ICU discharge. This review focuses on the neuropsychiatric aspects of PICS in ICU survivors including diagnostic, screening, and treatment recommendations. It also highlights the value of post-ICU clinics and the unique role of the consultation psychiatrist in the care of this patient population.The current American Society of Hematology (ASH) guidelines for the management of patients with immune thrombocytopenic purpura (ITP) are an update to the 2011 guidelines. The updates focus on treating patients with ITP without bleeding in both outpatient and inpatient settings, including those with newly diagnosed, persistent, and chronic ITP refractory to first-line therapy. Recommendations for therapy include corticosteroids, intravenous immunoglobulins, anti-D immunoglobulin, rituximab, splenectomy, and thrombopoietin-receptor agonists, as well as observation.

HPV-associated head and neck squamous cell carcinoma (HPV+HNSCC) is the most common HPV-associated malignancy in the United States and continues to increase in incidence. CI-1040 MEK inhibitor Current diagnostic approaches for HPV+HNSCC rely on tissue biopsy followed by histomorphologic assessment and detection of HPV indirectly by p16 IHC. Such approaches are invasive and have variable sensitivity.

We conducted a prospective observational study in 140 subjects (70 cases and 70 controls) to test the hypothesis that a noninvasive diagnostic approach for HPV+HNSCC would have improved diagnostic accuracy, lower cost, and shorter diagnostic interval compared with standard approaches. Blood was collected, processed for circulating tumor HPV DNA (ctHPVDNA), and analyzed with custom ddPCR assays for HPV genotypes 16, 18, 33, 35, and 45. Diagnostic performance, cost, and diagnostic interval were calculated for standard clinical workup and compared with a noninvasive approach using ctHPVDNA combined with cross-sectional imaging and physical examination findings.

Sensitivity and specificity of ctHPVDNA for detecting HPV+HNSCC were 98.4% and 98.6%, respectively. Sensitivity and specificity of a composite noninvasive diagnostic using ctHPVDNA and imaging/physical examination were 95.1% and 98.6%, respectively. Diagnostic accuracy of this noninvasive approach was significantly higher than standard of care (Youden index 0.937 vs. 0.707, P = 0.0006). Costs of noninvasive diagnostic were 36% to 38% less than standard clinical workup and the median diagnostic interval was 26 days less.

A noninvasive diagnostic approach for HPV+HNSCC demonstrated improved accuracy, reduced cost, and a shorter time to diagnosis compared with standard clinical workup and could be a viable alternative in the future.

A noninvasive diagnostic approach for HPV+HNSCC demonstrated improved accuracy, reduced cost, and a shorter time to diagnosis compared with standard clinical workup and could be a viable alternative in the future.Leiomyosarcoma (LMS) of the colon accounts for less then 1% of all colorectal malignancies. Our patient was a 72-year-old man with a history of aortic valvular disorder and congestive heart failure, who presented with an abdominal mass and no constitutional symptoms. The CT scan finding suggested a large tumour with both solid and cystic components. Intraoperatively, a portion of the involved colon was resected along with the tumour. Microscopically, the tumour was found to invade the muscularis propria layer of the transverse colon. The final diagnosis was LMS, FNCLCC grade 2 of 3 based on the histology and immunochemistry.