Τρίτη 18 Οκτωβρίου 2022

Adoption of adjuvant chemotherapy in high‐risk salivary gland malignancies

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Abstract

Background

The present study characterizes national trends in the utilization of adjuvant chemotherapy to treat salivary gland malignancies.

Methods

The National Cancer Database was queried for salivary gland malignancies treated by surgery with radiation in 2004–2019. Proportions of patients receiving adjuvant chemotherapy over the study period were analyzed by linear regression. The impact of chemotherapy on overall survival was assessed using Kaplan–Meier and Cox proportional hazards analyses.

Results

Among 15 965 patients meeting inclusion criteria, 2355 (14.8%) received adjuvant chemotherapy. Chemotherapy utilization significantly increased from 4.9% to 16.5% over the study period (p < 0.001). No survival benefit was observed with adjuvant chemotherapy on propensity score-matched Kaplan–Meier analysis (HR: 0.98; 95% CI: 0.86–1.11; p = 0.72) or multivariable Cox regression (HR: 0.92; 95% CI: 0.78–1.09; p = 0.34).

Conclusions

Adjuvant chemotherapy has been increasingly utilized to treat salivary gland malignancies in recent years. Our findings highlight the importance of obtaining high-quality prospective data regarding the benefit of chemotherapy.
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Microelectrodes and radiofrequency for transoral horizontal supraglottic laryngectomy in T3 tumors

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Abstract

The aim of this manuscript is to show the surgical technique for horizontal supraglottic laryngectomy in T3 carcinomas by a transoral approach using microelectrodes and radiofrequency. From 2009 to 2020, 11 selected cases of T3 laryngeal supraglottic carcinomas invading the pre-epiglottic space, with preserved vocal cords mobility underwent surgery. The technique is described step by step. Average time duration of the larynx surgery was 95 min. Nine percent of the patients presented a profuse hemorrhage 7 days postoperative; in 73% of patients the nasogastric feeding tube was withdrew 10 days after surgery. We emphasize a remarkable short surgical time and high hemostatic effectiveness. The ME tips allow to perform cuts at angles and contribute with a sense of touch. The low cost of the equipment and its easy handling and maintenance is a remarkable advantage over other technologies for transoral surgery.
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Tamoxifen Alters TGF‐β1/Smad Signaling in Vocal Fold Injury

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Tamoxifen Alters TGF-β1/Smad Signaling in Vocal Fold Injury

This study investigated the effects of tamoxifen on acute vocal fold injury in a preclinical model. The antifibrotic actions of tamoxifen appear to be mediated by transforming growth factor beta 1/Smad signaling providing a novel target for intervention.


Objectives

Effective treatments for vocal fold fibrosis remain elusive. Tamoxifen (TAM) is a selective estrogen receptor modulator and was recently reported to have antifibrotic actions. We hypothesized that TAM inhibits vocal fold fibrosis via altered transforming growth factor beta 1 (TGF-β1) signaling. Both in vitro and in vivo approaches were employed to address this hypothesis.

Methods

In vitro, vocal fold fibroblasts were treated with TAM (10−8 or 10−9 M) ± TGF-β1 (10 ng/ml) to quantify cell proliferation. The effects of TAM on genes related to fibrosis were quantified via quantitative real-time polymerase chain reaction. In vivo, rat vocal folds were unilaterally injured, and TAM was administered by oral gavage from pre-injury day 5 to post-injury day 7. The rats were randomized into two groups: 0 mg/kg/day (sham) and 50 mg/kg/day (TAM). Histological changes were examined on day 56 to assess tissue architecture.

Results

TAM (10−8 M) did not affect Smad3, Smad7, Acta2, or genes related to extracellular matrix metabolism. TAM (10−8 or 10−9 M) + TGF-β1, however, significantly increased Smad7 and Has3 expression and decreased Col1a1 and Acta2 expression compared to TGF-β1 alone. In vivo, TAM significantly increased lamina propria area, hyaluronic acid concentration, and reduced collagen deposition compared to sham treatment.

Conclusions

TAM has antifibrotic potential via the regulation of TGF-β1/Smad signaling in vocal fold injury. These findings provide foundational data to develop innovative therapeutic options for vocal fold fibrosis.

Level of Evidence

NA Laryngoscope, 2022
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Early maladaptive schemas and ICD‐11 CPTSD symptoms: Treatment considerations

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Abstract

Objectives

Early maladaptive schemas (EMS) can result from adverse interpersonal traumatic experiences. The ICD-11 updated the concept of disorders following traumatic experiences with the new disorder of complex post-traumatic stress disorder (CPTSD). There is now a need to develop and test interventions for CPTSD. An essential step in identifying interventions that are particularly relevant to the treatment of CPTSD is to explore psychological constructs associated more closely with CPTSD compared to PTSD. The current study explored the associations of EMS with PTSD and CPTSD.

Design

The sample consisted of 603 adults (mean age = 41.65, SD = 13.8), recruited through social media and e-mails, and who responded to an online questionnaire.

Methods

Participants completed measures of demographic, traumatic life events, EMS, PTSD and CPTSD symptoms.

Results

Overall, results suggest that participants with CPTSD present with higher schema elevations across all schemas compared to those with PTSD or no diagnosis. Secondly, the schemas of emotional deprivation, abandonment/instability, social isolation/alienation, defectiveness/shame, enmeshment/undeveloped self, subjugation, emotional inhibition and insufficient self-control/self-discipline were significantly associated with the symptom clusters of CPTSD. Finally, results indicate that different schemas form significant associations with the individual symptom clusters of CPTSD.

Conclusions

Although results require replication in clinical samples, initial findings suggest that specific EMS may be important psychological correlates of CPTSD symptoms. Wider treatment considerations of these findings are discussed.
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Estimation of monkeypox spread in a non‐endemic country considering contact tracing and self‐reporting: a stochastic modeling study

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Abstract

In May 2022, monkeypox started to spread in non-endemic countries. To investigate contact tracing and self-reporting of the primary case in the local community, a stochastic model is developed. An algorithm based on Gillespie's stochastic chemical kinetics is used to quantify the number of infections, contacts, and duration from the arrival of the primary case to the detection of the index case (or until there are no more local infections). Different scenarios were set considering the delay in contact tracing and behavior of infectors. We found that the self-reporting behavior of a primary case is the most significant factor affecting outbreak size and duration. Scenarios with a self-reporting primary case have an 86% reduction in infections (average: 5 to 7, in a population of 10,000) and contacts (average: 27 to 72) compared to scenarios with a non-self-reporting primary case (average number of infections and contacts: 27 to 72 and 197 to 537, respectively ). Doubling the number of close contacts per day is less impactful compared to the self-reporting behavior of the primary case as it could only increase the number of infections by 45%. Our study emphasizes the importance of the prompt detection of the primary case.

This article is protected by copyright. All rights reserved.
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Adequacy of protein and calorie delivery according to the expected calculated targets. A day‐by‐day assessment in critically ill patients undergoing enteral feeding

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Abstract

Background

In critically-ill patients requiring mechanical ventilation for longer than 48-72 hours enteral nutrition (EN) should be started early. Since EN alone may be unable to reach the target nutritional requirement, supplemental parenteral nutrition should be administered. This study aimed at describing the daily rate of administered calories and proteins according to the expected calculated targets. The impact of calorie adequacy, deficit or excess on relevant clinical outcomes was explored.

Methods

Retrospective cohort study in 217 cardiac-surgery patients admitted postoperatively in intensive care unit (ICU) and undergoing EN. The effective intake provided via EN, parenteral nutrition (PN), oral nutritional supplements (ONS) and non-nutritional calories (NNC) was documented for a maximum of 20 days. The administered/required calories and proteins ratios (KcalA/R, ProtA/R) were calculated daily. Patients receiving 80-100%, < 80 % or > 100% of KcalA/R and ProtA/R were identified. The association between mean KcalA/R between day 4-7 and 30-days mortality was explored.

Results

A mean KcalA/R ratio of 92.0±40.6% was ensured between days 4-20. During days 4-7 the 80-100% calorie target was achieved in 26.9% of patients, while 44.9% were below and 28.2% over this range. EN contributed for 47.1% and PN for 41.2% to the total energy intake. An increase in 30-days mortality risk was documented for patients exceeding 100% of KcalA/R ratio (adjusted-HR 5.2; 95% CI 1.1-23.9; p=0.035).

Conclusions

Despite a preliminary estimate of nutritional requirement, a steady daily optimal 80-100% KcalA/R was not ensured to all patients. EN contributed only partially to both energy and protein intakes so that PN was largely used to achieve the desired nutritional targets.

This a rticle is protected by copyright. All rights reserved.
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Hypermethylation of RASSF1A gene in pediatric rhabdoid tumor of the kidney and clear cell sarcoma of the kidney

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Abstract

Background

Among pediatric renal tumors, rhabdoid tumor of the kidney (RTK) and clear cell sarcoma of the kidney (CCSK) are rare and associated with an unfavorable prognosis, while congenital mesoblastic nephroma (CMN) is associated with a good prognosis. Methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) promoter has been reported to correlate with a poor prognosis in patients with Wilms tumors, while its methylation status is unclear in other types of pediatric renal tumors.

Method

DNA methylation of the RASSF1A promoter in several pediatric renal tumors was analyzed with pyrosequencing. In order to clarify the correlation between expression of RASSF1A and DNA methylation of its promoter, the RTK cell line was treated with 5-Aza-2′-deoxycytidine (5-Aza-dC). RASSF1A was overexpressed in the RTK cell line to evaluate its functional effects.

Results

Quantitative methylation analysis demonstrated hypermethylation in the RASSF1A promoter region in RTK and CCSK, but not CMN. The 5-Aza-dC treatment induced demethylation of the RASSF1A promoter as well as increased RASSF1A mRNA expression. The transduction of RASSF1A has an effect on the suppression of viability and proliferation of RTK cells.

Conclusion

DNA methylation-mediated deficiency of RASSF1A might be involved in the development and aggressiveness of some pediatric renal tumors and correlated with a poor prognosis.
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Shared understanding and social connection: Integrating approaches from social psychology, social network analysis, and neuroscience

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Abstract

Meaningfully connecting with others is critical to the well-being of individuals. What phenomena contribute to and stem from social connection? In this paper, we integrate emerging work that uses neuroimaging and social network analysis with theories that explore the links between shared reality and social connection. We highlight recent work suggesting that the extent to which people have aligned mental processing and shared subjective construals to those around them—as shown by neural similarity—is associated with both objective and subjective social connection. On the other hand, idiosyncrasies are linked to difficulties with social connection. We conclude by suggesting how the links between shared understanding and social connection can be productively used as a framework to study psychosocial phenomena of interest.
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The Role of Pelvic Floor Muscle Training on Low Anterior Resection Syndrome: A Multicenter Randomized Controlled Trial

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imageBackground and Objective: Total mesorectal excision (TME) for rectal cancer (RC) often results in significant bowel symptoms, commonly known as low anterior resection syndrome (LARS). Although pelvic floor muscle training (PFMT) is recommended in noncancer populations for treating bowel symptoms, this has been scarcely investigated in RC patients. The objective was to investigate PFMT effectiveness on LARS in patients after TME for RC. Methods: A multicenter, single-blind prospective randomized controlled trial comparing PFMT (intervention; n=50) versus no PFMT (control; n=54) 1 month following TME/stoma closure was performed. The primary endpoint was the proportion of participants with an improvement in the LARS category at 4 months. Secondary outcomes were: continuous LARS scores, ColoRectal Functioning Outcome scores, Numeric Rating Scale scores, stool diary items, and Short Form 12 scores; all assessed at 1, 4, 6, and 12 months. Results: The proportion of participants with an improvement in LARS category was statistically higher after PFMT compared with controls at 4 months (38.3% vs 19.6%; P=0.0415) and 6 months (47.8% vs 21.3%; P=0.0091), but no longer at 12 months (40.0% vs 34.9%; P=0.3897). Following secondary outcomes were significantly lower at 4 months: LARS scores (continuous, P=0.0496), ColoRectal Functioning Outcome scores (P=0.0369) and frequency of bowel movements (P=0.0277), solid stool leakage (day, P=0.0241; night, P=0.0496) and the number of clusters (P=0.0369), derived from the stool diary. No significant differences were found for the Numeric Rating Scale/quality of life scores. Conclusions: PFMT for bowel symptoms after TME resulted in lower proportions and faster recovery of bowel symptoms up to 6 months after surgery/stoma closure, justifying PFMT as an early, first-line treatment option for bowel symptoms after RC.
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Long-Term Oncological Outcomes After Colorectal Anastomotic Leakage: A Retrospective Dutch Population-based Study

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imageObjective: The aim was to evaluate the impact of anastomotic leak (AL) after colon cancer (CC) and rectal cancer (RC) surgery on 5-year relative survival, disease-free survival (DFS), and disease recurrence. Background: AL after CC and RC resection is a severe postoperative complication with conflicting evidence whether it deteriorates long-term outcomes. Methods: Patients with stage I to IV CC and RC who underwent resection with primary anastomosis were included from the Netherlands Cancer Registry (2008–2018). Relative survival, measured from day of resection, and multivariable relative excess risks (RERs) were analyzed. DFS and recurrence were evaluated in a subset with stage I to III patients operated in 2015. All analyses were performed with patients who survived 90 days postoperatively. Results: A total of 65,299 CC and 22,855 RC patients were included. Five-year relative survival after CC resection with and without AL was 95% versus 100%, 89% versus 94%, 66% versus 76%, and 28% versus 25% for stage I to IV disease. AL was associated with a significantly higher RER for death in stage II and III CC patients. Stage-specific 5-year relative survival in RC patients with and without AL was 97% versus 101%, 90% versus 95%, 74% versus 83%, and 32% versus 41%. AL was associated with a significantly higher RER for death in stage III and IV RC patients. DFS was significantly lower in CC patients with AL, but disease recurrence was not associated with AL after colorectal cancer resection. Conclusion: AL has a stage-dependent negative impact on survival in both CC and RC, but no independent association with disease recurrence.
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