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The concentration at half maximal D2 occupancy during transdermal patch applications, 0.857 ng/mL, was higher than that after oral doses, 0.112 ng/mL, suggesting metabolite contribution after oral doses. The median predicted D2 occupancy during blonanserin patch applications at doses of 40 and 80 mg/d was 48.7% and 62.5%, respectively, and the distribution of D2 occupancy at these doses could cover most of that at oral doses of 8 to 24 mg/d.
Predicted D2 occupancy suggested that a 40- to 80-mg/d blonanserin transdermal patch dose corresponds to an 8- to 24-mg/d oral dose for the treatment of schizophrenia.
Predicted D2 occupancy suggested that a 40- to 80-mg/d blonanserin transdermal patch dose corresponds to an 8- to 24-mg/d oral dose for the treatment of schizophrenia.
Chronic pain is the leading cause of disability worldwide and is strongly associated with the epidemic of opioid overdosing events. However, the causal links between chronic pain, opioid prescriptions, and mortality remain unclear.
This study included 13,884 US adults aged ≥20 years who provided data on chronic pain in the National Health and Nutrition Examination Survey 1999-2004 with linkage to mortality databases through 2015. We employed the generalized form of the front-door formula within the structural causal model framework to investigate the causal effect of chronic pain on all-cause mortality mediated by opioid prescriptions.
We identified a total of 718 participants at 3 years of follow-up and 1260 participants at 5 years as having died from all causes. Opioid prescriptions increased the risk of all-cause mortality with an estimated odds ratio (OR) (95% confidence interval) = 1.5 (1.1, 1.9) at 3 years and 1.3 (1.1, 1.6) at 5 years. The front-door formula revealed that chronic pain increased the risk of all-cause mortality through opioid prescriptions; OR = 1.06 (1.01, 1.11) at 3 years and 1.03 (1.01, 1.06) at 5 years. Our bias analysis showed that our findings based on the front-door formula were likely robust to plausible sources of bias from uncontrolled exposure-mediator or mediator-outcome confounding.
Chronic pain increased the risk of all-cause mortality through opioid prescriptions. Our findings highlight the importance of careful guideline-based chronic pain management to prevent death from possibly inappropriate opioid prescriptions driven by chronic pain.
Chronic pain increased the risk of all-cause mortality through opioid prescriptions. Our findings highlight the importance of careful guideline-based chronic pain management to prevent death from possibly inappropriate opioid prescriptions driven by chronic pain.
Aging and elevated activity of the renin-angiotensin-system (RAS) are associated with hypertension, vascular and emotional behavioral abnormalities, like anxiety and depression. Many actions of the main effector hormone of the RAS, angiotensin II (Ang II), are mediated by Ang II type 1 receptor whose activity is modulated by the regulator of G-protein signaling 5 (RGS5) protein. We assessed the role of RGS5 on blood pressure, vascular and emotional behavioral outcomes in aged male mice in the presence and absence of chronically elevated Ang II levels. We used aged (∼21-month old) male RGS5-deficient (RGS5 -/- ) and wild-type (RGS5 +/+ ) mice treated with vehicle (saline) or Ang II (1 mg/kg/d for 21 days). RGS5 deficiency increased baseline and cerebral vascular superoxide levels in the presence of chronically elevated Ang II levels, suggesting that RGS5 deficiency leads to elevated blood pressure and deleterious cerebral vascular outcomes in aged mice. RGS5 deletion had no effect on Ang II-induced increasesive effects on blood pressure and the cerebral vasculature in aged mice. Clinically, these data suggest that RAS blockers may significantly reduce cerebrovascular disease risk in aged males lacking RGS5.
There is a scarcity of information regarding the clinical characteristics of rare cutaneous malignancies in skin of color that has yet to be comprehensively explored.
To review and compile the racial differences in epidemiology, clinical presentation, histology, treatments, and outcomes of 3 rare skin cancers dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC).
Several searches with keywords denoting specific skin cancer type and race were conducted on PubMed to complete this narrative review.
We analyzed 50 sources that were relevant to the initial objective.
The literature demonstrates that there are nuances in DFSP, MCC, and SC unique to African Americans, Asians/Pacific Islanders, and Hispanics that may differ significantly from Caucasian counterparts. African Americans consistently suffer from the worst clinical outcomes in all 3 rare cutaneous malignancies reviewed. Greater physician awareness and knowledge of the discussed racial differences is the preliminary step to address these disparities.
The literature demonstrates that there are nuances in DFSP, MCC, and SC unique to African Americans, Asians/Pacific Islanders, and Hispanics that may differ significantly from Caucasian counterparts. African Americans consistently suffer from the worst clinical outcomes in all 3 rare cutaneous malignancies reviewed. Greater physician awareness and knowledge of the discussed racial differences is the preliminary step to address these disparities.
This study aimed to evaluate the prognostic value of metabolic parameters on 18F-FDG PET/CT and tumor dose (TD) on posttreatment 90Y PET/CT in patients with hepatocellular carcinoma (HCC) who underwent 90Y transarterial radioembolization (TARE).
Forty-seven HCC patients treated with 90Y TARE were retrospectively enrolled between January 2013 and October 2018. 18F-FDG PET/CT was performed before treatment. Maximum tumor SUV-to-mean normal liver SUV ratio (TLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured for each patient. Voxel dosimetry was performed on 90Y PET/CT images to measure TD. The prognostic significance of metabolic parameters on 18F-FDG PET/CT, TD on 90Y PET/CT, and clinical factors for overall survival (OS) was evaluated. In addition, TD on 90Y PET/CT was analyzed in relation to the administered dose of 90Y-labeled microspheres and metabolic parameters on 18F-FDG PET/CT.
The median patient age was 57 years, and 37 patients (78.7%) were men. During the followtive tumor volume on pretreatment 18F-FDG PET/CT, is a better prognostic factor than TD on 90Y PET/CT for predicting OS in HCC patients treated with 90Y TARE.
Transthyretin cardiac amyloidosis (ATTR and ATTRv) is an underrecognized cause of heart failure that results from myocardial deposition of misfolded protein (TTR or prealbumin). The diagnosis can be confirmed by uptake of 99m Tc-pyrophosphate ( 99m Tc-PYP) in the heart with serologic studies to rule out light chain disease. We present the case of a 70-year-old woman who underwent a 99m Tc-PYP scan. The patient had a large right-sided pleural effusion that lowered counts in the right chest on planar imaging, interfered with ratio-based grading of PYP uptake, and highlighted the importance of obtaining SPECT/CT for problem-solving in cases where uptake ratios may be spurious.
Transthyretin cardiac amyloidosis (ATTR and ATTRv) is an underrecognized cause of heart failure that results from myocardial deposition of misfolded protein (TTR or prealbumin). The diagnosis can be confirmed by uptake of 99m Tc-pyrophosphate ( 99m Tc-PYP) in the heart with serologic studies to rule out light chain disease. We present the case of a 70-year-old woman who underwent a 99m Tc-PYP scan. The patient had a large right-sided pleural effusion that lowered counts in the right chest on planar imaging, interfered with ratio-based grading of PYP uptake, and highlighted the importance of obtaining SPECT/CT for problem-solving in cases where uptake ratios may be spurious.Mesonephric-like adenocarcinoma (MLA) was introduced as a new tumor type in the endometrium and the ovary in the 2020 World Health Organization (WHO) Classification. This is a rare recently described (2016) and clinically aggressive carcinoma with a propensity for distant spread, especially to the lungs. MLA has a characteristic morphology and immunophenotype (hormone receptor negative; TTF1 and/or GATA3 positive). These neoplasms are commonly associated with KRAS and PIK3CA mutations and in the Cancer Genome Atlas (TCGA) molecular classification of endometrial carcinomas fall into the copy number low/no specific molecular profile category. Although they show significant morphological, immunophenotypic and molecular overlap with cervical mesonephric adenocarcinomas, there are other parameters which suggest a Mullerian origin and, as such, the term MLA seems apt. mTOR inhibitor MLA can be added to the list of endometriosis-associated ovarian neoplasms. In this paper, I outline the series of events which lead to the first description of MLA and review the subsequent literature on this tumor type which has expanded on the morphologic features and immunophenotype, discovered the molecular underpinnings and elucidated the clinical behavior. The discovery of MLA represents an example of "new" entities still to this day being discovered through careful morphologic observations and referral of cases for specialist opinion.
Xanthogranulomatous pyelonephritis is a rare disease that was often accompanied with urinary obstruction. The focal form of xanthogranulomatous pyelonephritis is frequently misdiagnosed as malignancy. Here we present FDG PET/CT findings of a case focal xanthogranulomatous pyelonephritis in a 66-year-old woman with polycystic liver and kidney disease. The image showed a polycystic mass in the inferior pole of right kidney with high FDG uptake in the cystic wall, which was suggestive of a cystic renal carcinoma. Right radical nephrectomy was subsequently performed. The postsurgical pathology revealed xanthogranulomatous pyelonephritis.
Xanthogranulomatous pyelonephritis is a rare disease that was often accompanied with urinary obstruction. The focal form of xanthogranulomatous pyelonephritis is frequently misdiagnosed as malignancy. Here we present FDG PET/CT findings of a case focal xanthogranulomatous pyelonephritis in a 66-year-old woman with polycystic liver and kidney disease. The image showed a polycystic mass in the inferior pole of right kidney with high FDG uptake in the cystic wall, which was suggestive of a cystic renal carcinoma. Right radical nephrectomy was subsequently performed. The postsurgical pathology revealed xanthogranulomatous pyelonephritis.
We report a case of tuberculosis peritonitis in a 26-year-old woman who presented with abdominal pain, fatigue, and weight loss for the last 4 months. Abdominal US and CT demonstrated intra-abdominal massive ascites, misty mesentery, and diffuse peritoneal thickening. In addition, 3 nodular lesions were detected in the right lung. 18 F-FDG PET/CT showed hypermetabolism in lung nodules, mesenteric area, peritoneal thickening, and ascites. 68 Ga-FAPI-04 (fibroblast activation protein-specific inhibitor) PET/CT imaging was also performed; high uptakes were detected in the same regions of 18 F-FDG PET/CT. Tuberculosis diagnosis was made after histopathological examination of wedge resection of the right lung.
We report a case of tuberculosis peritonitis in a 26-year-old woman who presented with abdominal pain, fatigue, and weight loss for the last 4 months. Abdominal US and CT demonstrated intra-abdominal massive ascites, misty mesentery, and diffuse peritoneal thickening. In addition, 3 nodular lesions were detected in the right lung.
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