Recent advances in microsurgery such as lymphaticovenous bypass (LVB) have been shown to decrease limb volumes and improve subjective symptoms in patients with lymphedema. However, to date, it ...remains unknown if these procedures can reverse the pathological tissue changes associated with lymphedema. Therefore, the purpose of this study was to analyze skin tissue changes in patients before and after LVB.
Matched skin biopsy samples were collected from normal and lymphedematous limbs of 6 patients with unilateral breast cancer-related upper extremity lymphedema before and 6 months after LVB. Biopsy specimens were fixed and analyzed for inflammation, fibrosis, hyperkeratosis, and lymphangiogenesis. Six months following LVB, 83% of patients had symptomatic improvement in their lymphedema. Histological analysis at this time demonstrated a significant decrease in tissue CD4(+) cell inflammation in lymphedematous limb (but not normal limb) biopsies (p<0.01). These changes were associated with significantly decreased tissue fibrosis as demonstrated by decreased collagen type I deposition and TGF-β1 expression (all p<0.01). In addition, we found a significant decrease in epidermal thickness, decreased numbers of proliferating basal keratinocytes, and decreased number of LYVE-1(+) lymphatic vessels in lymphedematous limbs after LVB.
We have shown, for the first time, that microsurgical LVB not only improves symptomatology of lymphedema but also helps to improve pathologic changes in the skin. These findings suggest that the some of the pathologic changes of lymphedema are reversible and may be related to lymphatic fluid stasis.
Highlights ► The CALM Program ( C oaching A pproach behavior and L eading by M odeling) is a 12-session modification of Parent–Child Interaction Therapy (PCIT) developed for the treatment of anxious ...youth between the ages of three and eight presenting with separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, and/or specific phobias. ► The present study examined the preliminary feasibility and efficacy of the CALM Program in a sample of anxious youth ages 4–8 years ( M = 5.4; N = 9). ► Roughly 80% of the sample completed all treatment sessions. All treatment completers were categorized as global treatment responders by independent evaluators, with all but one showing full diagnostic improvements, and all but one showing meaningful functional improvements. ► Findings lend preliminary support for the promising role of live parent coaching for the treatment of a range of anxiety disorders that present in early childhood.
Pediatric anxiety disorders are highly prevalent and impairing and are considered gateway disorders in that they predict adult psychiatric problems. Although they can be effectively treated in the ...short term, data are limited on the long-term outcomes in treated children and adolescents, particularly those treated with medication.
To determine whether acute clinical improvement and treatment type (i.e., cognitive behavioral therapy, medication, or their combination) predicted remission of anxiety and improvement in global functioning at a mean of 6 years after randomization and to examine predictors of outcomes at follow-up.
This naturalistic follow-up study, as part of the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), was conducted at 6 academic sites in the United States and included 288 youths (age range, 11-26 years; mean age, 17 years). Youths were randomized to 1 of 4 interventions (cognitive behavioral therapy, medication, combination, or pill placebo) in the Child/Adolescent Anxiety Multimodal Study (CAMS) and were evaluated a mean of 6 years after randomization. Participants in this study constituted 59.0% of the original CAMS sample.
Participants were assessed by independent evaluators using a semistructured diagnostic interview to determine the presence of anxiety disorders, the severity of anxiety, and global functioning. Participants and their parents completed questionnaires about mental health symptoms, family functioning, life events, and mental health service use.
Remission, defined as the absence of all study entry anxiety disorders. RESULTS Almost half of the sample (46.5%) were in remission a mean of 6 years after randomization. Responders to acute treatment were significantly more likely to be in remission (odds ratio, 1.83; 95% CI, 1.08-3.09) and had less severe anxiety symptoms and higher functioning; the assigned treatment arm was unrelated to outcomes. Several predictors of remission and functioning were identified.
Youths rated as responders during the acute treatment phase of CAMS were more likely to be in remission a mean of 6 years after randomization, although the effect size was small. Relapse occurred in almost half (48%) of acute responders, suggesting the need for more intensive or continued treatment for a sizable proportion of youths with anxiety disorders. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00052078.
The emergence of a clinically daptomycin-resistant Staphylococcus aureus isolate occurred during treatment of methicillin-resistant S. aureus bacteremia and probable vertebral osteomyelitis. The ...breakthrough isolate was indistinguishable from pretreatment daptomycin-susceptible isolates by pulsed-field gel electrophoresis. Daptomycin nonsusceptibility was confirmed by MIC and time-kill curve analyses.
Endothelin-converting enzyme-1 (ECE1) activates the endothelin-1 peptide, which upregulates pathways that are related to diverse hallmarks of cancer. ECE1 is expressed as four isoforms differing in ...their N-terminal domains. Protein kinase CK2 phosphorylates the N-terminus of isoform ECE1c, enhancing its stability and promoting invasiveness of colorectal cancer cells. However, the specific residues in ECE1c that are phosphorylated by CK2 and how this phosphorylation promotes invasiveness was unknown. Here we demonstrate that Ser-18 and Ser-20 are the
bona fide
residues phosphorylated by CK2 in ECE1c. Thus, biphospho-mimetic ECE1c
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and biphospho-resistant ECE1c
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mutants were constructed and stably expressed in different colorectal cancer cells through lentiviral transduction. Biphospho-mimetic ECE1c
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displayed the highest stability in cells, even in the presence of the specific CK2 inhibitor silmitasertib. Concordantly, ECE1c
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-expressing cells showed enhanced hallmarks of cancer, such as proliferation, migration, invasiveness, and self-renewal capacities. Conversely, cells expressing the less-stable biphospho-resistant ECE1c
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showed a reduction in these features, but also displayed an important sensitization to 5-fluorouracil, an antineoplastic agent traditionally used as therapy in colorectal cancer patients. Altogether, these findings suggest that phosphorylation of ECE1c at Ser-18 and Ser-20 by CK2 promotes aggressiveness in colorectal cancer cells. Therefore, phospho-ECE1c may constitute a novel biomarker of poor prognosis and CK2 inhibition may be envisioned as a potential therapy for colorectal cancer patients.
Hepatorenal Syndrome is a critical complication of liver failure, mainly in cirrhotic patients and rarely in patients with acute liver disease. It is a complex spectrum of conditions that leads to ...renal dysfunction in the liver cirrhosis population; the pathophysiology is characterized by a specific triad: circulatory dysfunction, nitric oxide (NO) dysfunction and systemic inflammation but a specific kidney damage has never been demonstrated, in a clinicopathological study, kidney biopsies of patients with cirrhosis showed a wide spectrum of kidney damage. In addition, the absence of significant hematuria or proteinuria does not exclude renal damage. It is estimated that 40% of cirrhotic patients will develop hepatorenal syndrome with in-hospital mortality of about one-third of these patients. The burden of the problem is dramatic considering the worldwide prevalence of more than 10 million decompensated cirrhotic patients, and the age-standardized prevalence rate of decompensated cirrhosis has gone through a significant rise between 1990 and 2017. Given the syndrome's poor prognosis, the clinician must know how to manage early treatment and any complications. The widespread adoption of albumin and vasopressors has increased Hepatorenal syndrome-acute kidney injury reversal and may increase overall survival, as previously shown. Further research is needed to define whether the subclassification of patients may allow to find a personalized strategy to treat Hepatorenal Syndrome and to define the role of new molecules and extracorporeal treatment may allow better outcomes with a reduction in treatment-related adverse effects. This review aims to examine both pharmacological and non-pharmacological treatment of hepatorenal syndrome, with a particular focus on managing adverse events caused by treatment.
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