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Cancers Jun 2024Patients with advanced vulvoperineal cancer require a multidisciplinary treatment approach to ensure oncological safety, timely recovery, and the highest possible... (Review)
Review
BACKGROUND
Patients with advanced vulvoperineal cancer require a multidisciplinary treatment approach to ensure oncological safety, timely recovery, and the highest possible quality of life (QoL). Reconstructions in this region often lead to complications, affecting approximately 30% of patients. Flap design has evolved towards perforator-based approaches to reduce functional deficits and (donor site) complications, since they allow for the preservation of relevant anatomical structures. Next to their greater surgical challenge in elevation, their superiority over non-perforator-based approaches is still debated.
METHODS
To compare outcomes between perforator and non-perforator flaps in female vulvoperineal reconstruction, we conducted a systematic review of English-language studies published after 1980, including randomized controlled trials, cohort studies, and case series. Data on demographics and surgical outcomes were extracted and classified using the Clavien-Dindo classification. We used a random-effects meta-analysis to derive a pooled estimate of complication frequency (%) in patients who received at least one perforator flap and in patients who received non-perforator flaps.
RESULTS
Among 2576 screened studies, 49 met our inclusion criteria, encompassing 1840 patients. The overall short-term surgical complication rate was comparable in patients receiving a perforator ( = 276) or a non-perforator flap ( = 1564) reconstruction (* > 0.05). There was a tendency towards fewer complications when using perforator flaps. The assessment of patients' QoL was scarce.
CONCLUSIONS
Vulvoperineal reconstruction using perforator flaps shows promising results compared with non-perforator flaps. There is a need for the assessment of its long-term outcomes and for a systematic evaluation of patient QoL to further demonstrate its benefit for affected patients.
PubMed: 38927919
DOI: 10.3390/cancers16122213 -
Cancers Jun 2024Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due...
Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome (GS), is a genetic disorder characterized by the development of multiple cutaneous BCCs due to mutations in the hedgehog signaling pathway. The use of hedgehog pathway inhibitors-vismodegib and sonidegib-has emerged as a promising therapeutic strategy for managing BCCs in individuals with GS. In a retrospective study conducted between March 2012 and January 2024, a cohort of 16 Gorlin syndrome patients who received treatment with either sonidegib or vismodegib were analyzed. The primary objectives of the study were to evaluate the efficacy, safety profile, and duration of response to oral hedgehog inhibitors in this patient population. The study assessed various parameters, including the number of new BCCs that developed before and after treatment initiation, the duration and sustainability of treatment responses, as well as the incidence of adverse effects associated with hedgehog inhibitor therapy. The findings of the study revealed that sustained treatment with hedgehog inhibitors could effectively suppress the progression of both new and existing BCCs. Furthermore, the results indicated that sonidegib exhibited superior efficacy and safety compared to vismodegib in the treatment of BCCs in individuals with GS. Notably, adjustments to the administration schedule of sonidegib were found to improve tolerability without compromising therapeutic efficacy, potentially leading to prolonged durations of treatment response and disease control.
PubMed: 38927872
DOI: 10.3390/cancers16122166 -
Bioengineering (Basel, Switzerland) May 2024The internal mechanisms of dental air turbine handpieces (DATHs) have become increasingly intricate over time. To enhance the operational reliability of dental...
The internal mechanisms of dental air turbine handpieces (DATHs) have become increasingly intricate over time. To enhance the operational reliability of dental procedures and guarantee patient safety, this study formulated temporal convolution network (TCN) prediction models with the functions of causality in time sequence, transmitting memory, learning, storing, and fast convergence for monitoring the health and diagnosing the rotor and collet failure of DATHs. A handpiece mimicking a dentist's hand load of 100 g was employed to repeatedly mill a glass porcelain block back and forth for cutting. An accelerometer was employed to capture vibration signals during free-running of unrestrained operation of the handpiece, aiming to discern the characteristic features of these vibrations. These data were then utilized to create a diagnostic health classification (DHC) for further developing a TCN, a 1D convolutional neural network (CNN), and long short-term memory (LSTM) prediction models. The three frameworks were used and compared for machine learning to establish DHC prediction models for the DATH. The experimental results indicate that, in terms of DHC predicted for the experimental dataset, the square categorical cross-entropy loss function error of the TCN framework was generally lower than that of the 1D CNN, which did not have a memory framework or the drawback of the vanishing gradient problem. In addition, the TCN framework outperformed the LSTM model, which required a longer history to provide sufficient diagnostic ability. Still, high accuracies were achieved both in the direction of feed-drive milling and in the gravity of the handpiece through vibration signals. In general, the failure classification prediction model could accurately predict the health and failure mode of the dental handpiece before the use of the DATH when an embedded sensor was available. Therefore, this model could prove to be a beneficial tool for predicting the deterioration patterns of real dental handpieces in their remaining useful life.
PubMed: 38927791
DOI: 10.3390/bioengineering11060555 -
Biomedicines Jun 2024Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body's own innate bactericidal mechanisms. It also provides...
Xylitol is considered a naturally occurring antibacterial agent. It is generally believed to enhance the body's own innate bactericidal mechanisms. It also provides anti-adhesive effects against both Streptococcus pneumoniae and Haemophilus influenza. This study was performed to evaluate the efficacy and safety of xylitol nasal irrigation in the postoperative care of functional endoscopic sinus surgery (FESS). Patients with chronic rhinosinusitis who received FESS were recruited and randomly assigned to two groups at one month post-surgery. Thirty-five patients in the xylitol group received 400 mL of 5% xylitol nasal irrigation daily for 2 months, while another 35 in the normal saline (NS) group received 400 mL of NS nasal irrigation daily for 2 months. Prior to FESS, as well as before and after nasal irrigation, sinonasal symptoms were assessed through the 22-item Sino-Nasal Outcome Test Questionnaire. The patients also underwent an endoscopic examination while undergoing nasal function tests, and a cytokine measurement of the nasal lavage and a bacterial culture from the middle meatus were performed. The safety of the nasal irrigation was assessed through any self-reported adverse events, the Eustachian Tube Dysfunction Patient Questionnaire and the eustachian tube function test. The endoscopic scores and olfactory threshold significantly decreased after xylitol irrigation when compared with those before irrigation. The prevalence of Staphylococcus aureus in the nasal secretions also decreased significantly after xylitol irrigation. The amounts of Interleukin-5 and Interleukin-17A were significantly increased in the nasal lavage after xylitol irrigation. No side effects, including those related to eustachian tube function, were seen after nasal irrigation in both groups. Our results showed that xylitol nasal irrigation was both beneficial and safe during the postoperative care of FESS.
PubMed: 38927584
DOI: 10.3390/biomedicines12061377 -
Biomedicines Jun 2024The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of... (Review)
Review
BACKGROUND AND OBJECTIVES
The efficacy and safety of PD-L1 inhibitors in the treatment of cervical cancer is an ongoing research question. This review aims to establish a clear profile of atezolizumab, examining its impact on survival outcomes, response rates, and safety measured by serious adverse events (SAEs).
MATERIALS AND METHODS
A literature search was conducted using PubMed, Scopus, and Web of Science, focusing on articles published up to February 2024. The review followed the PRISMA guidelines and synthesized outcomes from four randomized trial studies involving atezolizumab administered at 1200 mg IV every three weeks, alone or in combination with chemoradiotherapy.
RESULTS
A total of 284 patients received atezolizumab, the majority being advanced stage cervical cancer (IVA-IVB). Median follow-up times ranged from 9 weeks to 32.9 months. It was found that combining atezolizumab with standard therapies extended median progression-free survival (PFS) from 10.4 to 13.7 months and overall survival (OS) from 22.8 to 32.1 months, according to the phase III trial. Monotherapy and initial treatment settings with atezolizumab also showed promising efficacy, with disease-free survival rates at 24 months reaching 79% compared to 52% with standard therapy alone. However, the treatment was associated with high rates of SAEs, reaching up to 79% in more intensive treatment combinations.
CONCLUSIONS
Atezolizumab demonstrates significant potential in improving PFS and OS in patients with cervical cancer, supporting its inclusion as a first-line treatment option. Despite the efficacy benefits, the high incidence of SAEs necessitates careful patient selection and management strategies to mitigate risks. This systematic review supports the continued evaluation of atezolizumab in broader clinical trials to refine its therapeutic profile and safety measures in the context of cervical cancer treatment.
PubMed: 38927498
DOI: 10.3390/biomedicines12061291 -
Biomedicines Jun 2024Infiltrating gliomas are challenging to treat, as the blood-brain barrier significantly impedes the success of therapeutic interventions. While some clinical trials for... (Review)
Review
Infiltrating gliomas are challenging to treat, as the blood-brain barrier significantly impedes the success of therapeutic interventions. While some clinical trials for high-grade gliomas have shown promise, patient outcomes remain poor. Microbubble-enhanced focused ultrasound (MB-FUS) is a rapidly evolving technology with demonstrated safety and efficacy in opening the blood-brain barrier across various disease models, including infiltrating gliomas. Initially recognized for its role in augmenting drug delivery, the potential of MB-FUS to augment liquid biopsy and immunotherapy is gaining research momentum. In this review, we will highlight recent advancements in preclinical and clinical studies that utilize focused ultrasound to treat gliomas and discuss the potential future uses of image-guided precision therapy using focused ultrasound.
PubMed: 38927437
DOI: 10.3390/biomedicines12061230 -
Antibiotics (Basel, Switzerland) Jun 2024Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure...
Previous studies have demonstrated the association between antibiotic use and severe COVID-19 outcomes. This study aimed to explore detailed antibiotic exposure characteristics among COVID-19 patients. Using the OpenSAFELY platform, which integrates extensive health data and covers 40% of the population in England, the study analysed 3.16 million COVID-19 patients with at least two prior antibiotic prescriptions. These patients were compared to up to six matched controls without hospitalisation records. A machine learning model categorised patients into ten groups based on their antibiotic exposure history over the three years before their COVID-19 diagnosis. The study found that for COVID-19 patients, the total number of prior antibiotic prescriptions, diversity of antibiotic types, broad-spectrum antibiotic prescriptions, time between first and last antibiotics, and recent antibiotic use were associated with an increased risk of severe COVID-19 outcomes. Patients in the highest decile of antibiotic exposure had an adjusted odds ratio of 4.8 for severe outcomes compared to those in the lowest decile. These findings suggest a potential link between extensive antibiotic use and the risk of severe COVID-19. This highlights the need for more judicious antibiotic prescribing in primary care, primarily for patients with higher risks of infection-related complications, which may better offset the potential adverse effects of repeated antibiotic use.
PubMed: 38927232
DOI: 10.3390/antibiotics13060566 -
Biomolecules Jun 2024The increasing utilization of Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) in managing type 2 diabetes mellitus has raised interest regarding their impact on... (Review)
Review
The increasing utilization of Glucagon-like Peptide-1 receptor agonists (GLP-1 RAs) in managing type 2 diabetes mellitus has raised interest regarding their impact on thyroid function. In fact, while these agents are well known for their efficacy in glycemic control and weight management, their association with thyroid disorders requires clarification due to the complex interplay between thyroid hormones and metabolic pathways. Thyroid dysfunction commonly co-occurs with metabolic conditions such as diabetes and obesity, suggesting a profound interconnection between these systems. This review aims to contribute to a deeper understanding of the interaction between GLP-1 RAs and thyroid dysfunction and to clarify the safety of GLP-1 RAs in diabetic patients with thyroid disorders. By synthesizing existing evidence, this review highlights that, despite various studies exploring this topic, current evidence is inconclusive, with conflicting results. It is important to note that these drugs are relatively recent, and longer-term studies with larger sample sizes are likely needed to draw clearer conclusions. Currently, no existing guidelines provide definitive directions on this clinical issue; however, it is advisable to include thyroid function tests in the routine screening of diabetic patients, particularly those treated with GLP-1 Ras, with the goal of optimizing patient care and management.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Thyroid Gland; Diabetes Mellitus, Type 2; Thyrotropin; Hypoglycemic Agents; Neoplasms; Thyroid Neoplasms
PubMed: 38927090
DOI: 10.3390/biom14060687 -
Epilepsia Open Jun 2024To investigate the Italian experience on the surgical and radiosurgical treatment of drug-resistant epilepsy due to hypothalamic hamartoma (HH) in the period 2011-2021...
OBJECTIVE
To investigate the Italian experience on the surgical and radiosurgical treatment of drug-resistant epilepsy due to hypothalamic hamartoma (HH) in the period 2011-2021 in six Italian epilepsy surgery centers, and to compare safety and efficacy profiles of the different techniques.
METHODS
We collected pseudo-anonymized patient's data with at least 12 months of follow-up. Surgical outcome was defined according to Engel classification of seizure outcome. Univariate analysis was performed to assess the risk of post-operative seizures, categorized in dichotomous variable as favorable and unfavorable; explanatory variables were considered. Mann-Whitney or Chi-squared test were used to assess the presence of an association between variables (p < 0.05).
RESULTS
Full presurgical and postoperative data about 42 patients from 6 epilepsy surgery centers were gathered. Engel class I was reached in the 65.8% and 66.6% of patients with gelastic and non-gelastic seizures, respectively. Other than daily non-gelastic seizures were associated with seizure freedom (p = 0.01), and the radiological type presented a trend toward significance (p = 0.12).
SIGNIFICANCE
Endoscopic disconnection and laser interstitial thermal therapy are effective in the treatment of HH-related epilepsy, with a tolerable safety profile. Both gelastic and non-gelastic seizures can be treated, also in patients with a long history of seizures.
PLAIN LANGUAGE SUMMARY
This study collected data about 42 patients with HH-related epilepsies. Endoscopic disconnection and laser therapy are both effective and safe in the treatment of hypothalamic hamartoma-related epilepsies.
PubMed: 38926936
DOI: 10.1002/epi4.12989 -
Translational Neurodegeneration Jun 2024The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer's Disease (AD) and to testing new drugs, with the... (Review)
Review
The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer's Disease (AD) and to testing new drugs, with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments, such as non-invasive stimulation techniques on AD neuropathology and symptoms. Among the different non-invasive brain stimulation approaches, transcranial alternating current stimulation (tACS) is gaining particular attention due to its ability to externally control gamma oscillations. Here, we outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD, applied specifically at 40 Hz frequency, and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.
Topics: Alzheimer Disease; Humans; Transcranial Direct Current Stimulation; Disease Progression; Gamma Rhythm; Animals
PubMed: 38926897
DOI: 10.1186/s40035-024-00423-y