Subtotal Versus Total Parathyroidectomy for the Management of Tertiary Hyperparathyroidism: A Systematic Literature Review and Meta-Analysis of Optimal Surgical Modality.

Background: Surgery is the definitive treatment option for tertiary hyperparathyroidism (THPT), however, the optimal surgical approach remains unclear. We aimed to compare total parathyroidectomy (PTX) with auto-transplantation vs subtotal PTX for THPT through a systematic review and meta-analysis.Methods: PubMed, Embase, and Web of Science were searched for studies comparing outcomes of total vs subtotal PTX for THPT. A total of 28 studies (n = 1000 patients) met the inclusion criteria.Results: The mean age was 46.5 years and 53% were female. The proportion of females (59% vs 49%) was higher in the total PTX with auto-transplantation cohort (P = .008). Both procedures had similar preoperative calcium and PTH levels. Postoperative and 6-month calcium and PTH were also comparable between groups, except transiently higher post-operative PTH in the total PTX with auto-transplantation cohort (P = .03). Hypercalcemia cure rates were 98%-100% with no difference between surgical techniques (P = .67). Safety profiles were comparable and low.Conclusions: Total PTX with auto-transplantation and subtotal PTX yield similar efficacy and safety for THPT, with no significant differences in cure rates, recurrence, complications, or biochemical control.

The Prevalence and Prognostic Implications of BRAF K601E Mutations in Thyroid Neoplasms: A Systematic Review and Meta-Analysis.

BACKGROUND: Activating mutations in the BRAF oncogene occur in 45% of papillary thyroid carcinomas (PTCs). Though less studied, K601E may identify a clinically distinct subset of thyroid neoplasms. METHODS: A bioinformatics assessment was conducted using the COSMIC database and in silico data analysis. A systematic search was conducted through August 2024 to identify studies reporting BRAF mutation in thyroid neoplasms. Pooled prevalence, histopathological subtype distribution, extrathyroidal extension, lymph node metastasis, recurrence, and survival were extracted/analyzed from 32 studies (13 191 patients). RESULTS: In the COSMIC database, BRAF K601E was found in various tissue types but mainly in the thyroid. In silico data analysis revealed a structural and functional basis for differences between K601E and V600E. Upon systematic review, the BRAF K601E mutation was identified in 2.8% of PTCs compared to 22% with V600E. The stratified analysis revealed geographical differences, with higher rates in Italy (5.23%) and the United States of America (3.31%). The K601E mutant was enriched for follicular-patterned variants like NIFTP (11.2% of cases). Meta-analysis demonstrated significantly reduced extrathyroidal extension for K601E versus V600E mutants (RR = 0.22, 95% CI = 0.10-0.50, p = 0.0003). CONCLUSION: K601E-mutated neoplasms could be a unique clinicopathological entity associated with low-risk histology and reduced extrathyroidal extension, consistent with a more indolent course than V600E mutants. Although detecting K601E may potentially guide conservative management, further prospective studies are needed.

Income Disparities Have a Significant Impact on Thyroid Cancer Recurrence and Survival.

PURPOSE: Income inequality profoundly impacts cancer outcomes, yet its specific effects on thyroid cancer remain unclear. Elucidating the influence of socioeconomic disparities is imperative to advance health equity and optimize patient care. This study evaluates associations between median household income and thyroid cancer recurrence and survival using national cancer registry data. METHODS: 139,302 thyroid cancer patients undergoing surgery from 2000-2019 were analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized by median annual household income at the county level (> or <$75,000). Multivariable regression determined the impact of income on recurrence and overall mortality. RESULTS: Higher-income patients had 26% lower recurrence odds (OR 0.74, 95%CI 0.55-0.99, p=0.042) and longer median survival (18.1 vs 17.7 years, p<0.001) compared to lower-income patients. On multivariate analysis, high income remained an independent predictor of reduced mortality after adjusting for demographics, tumor factors, and treatment (adjusted HR=0.84, 95%CI=0.81-0.87, p<0.001). Cancer-directed surgery (HR=0.28, 95%CI=0.26-0.30, p<0.001) and radioactive iodine (HR=0.69, 95%CI=0.66-0.71, p<0.001) were associated with lower mortality risk. CONCLUSIONS: Income disparities have a significant influence on thyroid cancer outcomes, including lower recurrence and reduced mortality. Targeting socioeconomic inequity could substantially reduce recurrence, improve survival, and promote health equity for all patients.

The HCV-Melanoma Paradox: First Multi-Cohort and Molecular Net-Work Analysis Reveals Lower Incidence but Worse Outcomes-Integrating Clinical, Real-World, and In Silico Data.

Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443-0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189-1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions: While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.

An international film dosimetry intercomparison to establish a multi-center audit framework.

BACKGROUND: In 2021, a Technical Meeting was hosted by the International Atomic Energy Agency (IAEA) where it was recommended that a standardized method for assessing the accuracy of film dose calculations should be established. PURPOSE: To design an audit that evaluates the accuracy of film dosimetry processes. To propose a framework for identifying out-of-tolerance results and to perform an international pilot study to test the audit design. METHODS: Six members of an international Dosimetry Audit Network (DAN) developed an audit for radiochromic film dosimetry. A single host center provided the materials to each participating DAN member to conduct the audits. Materials included: (1) a set of two irradiated audit films (10 Sq: 10 cm × 10 cm, 15 Sq: 15 cm × 15 cm), (2) a reference calibration film set, and (3) a blank sheet of film. The participants were blinded to the dose and tasked with producing dose maps using their standard film dosimetry process. Average Region-Of-Interest (ROI: 2 cm × 2 cm) dose was measured from the dose maps and compared to the known dose. In the audit, all participants used their local scanning and software protocols. Film calibration was performed in two distinct ways: (1) using a calibration film set which was provided by the host center and (2) using a calibration film set which was locally irradiated. Several variations of the audit were also performed to examine how scanning and software processing can affect film dosimetry results. In the first variation of the audit (VariantA), a set of film scans was processed using five different software solutions. In the second variation of the audit (VariantB), all films were scanned on the same scanner and processed using two in-house software solutions. RESULTS: Taking one film scan from each participant, the standard deviations (1σ) (SD) in the dose returned from the host calibration and returned from the local calibration were ±7.2% and ±6.5% respectively, with variations from -12.4% to 12.9% of the known dose. The larger dose variations in the data set were attributed to the corrections applied for variations in scanner brightness during processing and incorrectly assigned calibration doses. When the raw image data set was processed by an expert user of each software solution (VariantA) the SDs were ±2.7% and ±3.7% for in-house and vendor-based software, respectively. When the films were scanned on a single scanner and processed with the two in-house software solutions (VariantB) the results had a SD of ±2.3%. CONCLUSIONS: An audit has been designed and tested for radiotherapy film dosimetry at an international level. A framework for diagnosing issues within a film dosimetry process has been proposed that could be used to audit centers that use film as a dosimeter. Incorporating quality assurance throughout the film process is important in obtaining accurate and consistent film dosimetry. A better understanding of vendor-based software systems is necessary for users to process accurate and consistent film dosimetry.

Tools and recommendations for commissioning and quality assurance of deformable image registration in radiotherapy.

Multiple tools are available for commissioning and quality assurance of deformable image registration (DIR), each with their own advantages and disadvantages in the context of radiotherapy. The selection of appropriate tools should depend on the DIR application with its corresponding available input, desired output, and time requirement. Discussions were hosted by the ESTRO Physics Workshop 2021 on Commissioning and Quality Assurance for DIR in Radiotherapy. A consensus was reached on what requirements are needed for commissioning and quality assurance for different applications, and what combination of tools is associated with this. For commissioning, we recommend the target registration error of manually annotated anatomical landmarks or the distance-to-agreement of manually delineated contours to evaluate alignment. These should be supplemented by the distance to discordance and/or biomechanical criteria to evaluate consistency and plausibility. Digital phantoms can be useful to evaluate DIR for dose accumulation but are currently only available for a limited range of anatomies, image modalities and types of deformations. For quality assurance of DIR for contour propagation, we recommend at least a visual inspection of the registered image and contour. For quality assurance of DIR for warping quantitative information such as dose, Hounsfield units or positron emission tomography-data, we recommend visual inspection of the registered image together with image similarity to evaluate alignment, supplemented by an inspection of the Jacobian determinant or bending energy to evaluate plausibility, and by the dose (gradient) to evaluate relevance. We acknowledge that some of these metrics are still missing in currently available commercial solutions.

Radioactive iodine ablation therapy reduces the risk of recurrent disease in pediatric differentiated thyroid carcinoma.

BACKGROUND: While radioactive iodine (RAI) therapy in older adults with differentiated thyroid carcinoma (DTC) reduces recurrence, data in pediatrics remain limited. We conducted a meta-analysis to quantify outcomes and recurrence risk with RAI versus thyroidectomy alone in the pediatric population. METHODS: Systematic literature review identified 34 retrospective studies including 2913 DTC patients under age 22 years (published 2005-2023). Meta-analysis calculated pooled rates of disease persistence and recurrence. Relative risk ratios compared odds of recurrence with RAI versus no RAI. RESULTS: Patients had mean age 14.7 years (95 % CI, 14.2-15.2) and were 75.9 % female (95 % CI, 73.8-78.1 %). Majority (90.2 %) received RAI. Pooled persistence rate was 30.3 % (95 % CI, 21.7-39.5 %); higher with RAI (31.5 %; 95 % CI, 22.4-41.3 %) than no RAI (4.5 %; 95 % CI, 0.0-18.7 %) (OR 3.28; 95 % CI,1.82-5.91; p < 0.001). Recurrence rate was 8.97 % (95 % CI, 4.78-14.3 %). Those with RAI had 53.1 % lower recurrence risk versus no RAI (RR 0.47; 95 % CI, 0.27-0.82; p = 0.007). Median follow-up was 7.2 years (95 % CI, 5.8-8.5 years), with no association between follow-up duration and recurrence (r = -0.053; p = 0.80). CONCLUSIONS: RAI therapy as an adjunct to thyroidectomy is associated with a significantly lower risk of long-term recurrence in pediatric DTC. These findings advocate for the use of RAI in preventing recurrence among high-risk pediatric patients with DTC.

Reviving ancient therapeutics in modern medicine: an immunological and biological narrative review of wet cupping in the management of Hashimoto's thyroiditis.

Background and Objective: The interwoven immunological, biological, and genetic complexity of thyroid diseases makes suitable targeted therapies particularly challenging to develop. Stemming from ancient practices, al-hijamah, or wet cupping, has achieved notable popularity in recent years, leading to unique applications in modern medicine. By grappling with the current literature that links the effects of wet cupping with the immune system in patients with Hashimoto's thyroiditis (HT), this narrative review aims to compose a comprehensive assessment of this adjunctive treatment based on evidence of its integration into practice. Methods: Between upregulating critical players of the innate immune system, such as immunostimulatory cytokines, white blood cells (WBCs) and natural killer (NK) cells, and downregulating essential thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) and inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), wet cupping practices provide promising complementary therapy for hypothyroidism. Key Content and Findings: Wet cupping manipulates in vivo molecular mechanisms, as outlined in hemodynamic and microparticle clearance theories, to slow disease progression and even development in disease-free populations. Given the established utilization of wet cupping in the context of autoimmune diseases and inflammatory conditions, the emerging utility of wet cupping continues to gain credibility. Conclusions: This literature review illuminates the documented improvements in immune and biological function due to cupping therapeutic practices and sheds light on its appropriate application in the clinical setting for patients with HT. Furthermore, this review proposes a clear need for implementing future clinical trials, which may effectively bridge pathophysiological causes of hypothyroidism with underrated techniques for enhanced thyroid health.

Beyond Glycemic Control: GLP-1 Receptor Agonists and Their Impact on Calcium Homeostasis in Real-World Patients.

Background/Objectives: The effect of glucagon-like peptide-1 receptor (GLP-1R) agonists on calcium homeostasis is poorly understood. This study aimed to investigate the association between GLP-1R agonist use and the risk of hypocalcemia and/or hypercalcemia, as well as other clinical outcomes. Methods: A retrospective cohort study used de-identified patient data from the TriNetX Global Collaborative Network, including 15,655 adult patients prescribed GLP-1R agonists and 15,655 propensity-matched controls. Outcomes included hypocalcemia, hypercalcemia, emergency visits, hospitalizations, cardiovascular events, and all-cause mortality. Results: GLP-1R agonist use was associated with a reduced risk of hypocalcemia (2.7% vs. 5.5%, RR 0.49, 95% CI: 0.44-0.55) but an increased risk of hypercalcemia (2.3% vs. 1.1%, RR 2.02, 95% CI: 1.69-2.42). The effect on hypocalcemia was most pronounced during the first six months of treatment. Among individual agents, tirzepatide showed the most pronounced effect, reducing hypocalcemia risk by 63% while increasing hypercalcemia risk by 85%. Semaglutide demonstrated similar effects, while dulaglutide and liraglutide showed modest effects. Furthermore, GLP-1R agonist use was associated with reduced risks of emergency visits (RR 0.57, 95% CI: 0.54-0.60), hospitalizations (RR 0.40, 95% CI: 0.36-0.44), cardiovascular events, and all-cause mortality (HR 0.27, 95% CI: 0.21-0.36). Conclusions: GLP-1R agonists exhibit a complex influence on calcium homeostasis, reducing hypocalcemia risk while increasing hypercalcemia risk. Beyond calcium regulation, these medications significantly reduce healthcare utilization, improve cardiovascular outcomes, and decrease mortality. Further research is needed to elucidate the mechanisms behind the differential effects of individual GLP-1R agonists, particularly tirzepatide, to optimize personalized treatment approaches and long-term safety.

Characterisation of 3D-printable thermoplastics to be used as tissue-equivalent materials in photon and proton beam radiotherapy end-to-end quality assurance devices.

Objective.To investigate the potential of 3D-printable thermoplastics as tissue-equivalent materials to be used in multimodal radiotherapy end-to-end quality assurance (QA) devices.Approach.Six thermoplastics were investigated: Polylactic Acid (PLA), Acrylonitrile Butadiene Styrene (ABS), Polyethylene Terephthalate Glycol (PETG), Polymethyl Methacrylate (PMMA), High Impact Polystyrene (HIPS) and StoneFil. Measurements of mass density (ρ), Relative Electron Density (RED), in a nominal 6 MV photon beam, and Relative Stopping Power (RSP), in a 210 MeV proton pencil-beam, were performed. Average Hounsfield Units (HU) were derived from CTs acquired with two independent scanners. The calibration curves of both scanners were used to predict averageρ,RED and RSP values and compared against the experimental data. Finally, measured data ofρ,RED and RSP was compared against theoretical values estimated for the thermoplastic materials and biological tissues.Main results.Overall, goodρand RSP CT predictions were made; only PMMA and PETG showed differences >5%. The differences between experimental and CT predicted RED values were also <5% for PLA, ABS, PETG and PMMA; for HIPS and StoneFil higher differences were found (6.94% and 9.42/15.34%, respectively). Small HU variations were obtained in the CTs for all materials indicating good uniform density distribution in the samples production. ABS, PLA, PETG and PMMA showed potential equivalency for a variety of soft tissues (adipose tissue, skeletal muscle, brain and lung tissues, differences within 0.19%-8.35% for all properties). StoneFil was the closest substitute to bone, but differences were >10%. Theoretical calculations of all properties agreed with experimental values within 5% difference for most thermoplastics.Significance.Several 3D-printed thermoplastics were promising tissue-equivalent materials to be used in devices for end-to-end multimodal radiotherapy QA and may not require corrections in treatment planning systems' dose calculations. Theoretical calculations showed promise in identifying thermoplastics matching target biological tissues before experiments are performed.

Evaluating the Efficacy and Safety of Robotic Versus Conventional Completion Thyroidectomy: A 10-year Experience.

BACKGROUND: Robotic thyroidectomy is gaining popularity, yet its role in completion thyroidectomy remains unclear. We aimed to compare robotic vs conventional completion thyroidectomy for thyroid nodules. METHODS: This retrospective study analyzed patients undergoing completion thyroidectomy from 2010-2020, either by conventional open technique (n = 87) or a robotic remote-access approach (n = 44). Outcomes were compared between groups. RESULTS: A total of 131 patients were included. The robotic cohort was younger (45.3 ± 14.0 vs 55.5 ± 14.5 years, P < 0.001) with a lower BMI (25.9 ± 5.5 vs 33.7 ± 7.8 kg/m2, P < 0.001). Operative time was longer for robotic procedures (139 min vs 99 min, P < 0.001). Hospital stay was shorter after robotic surgery, with 25% discharged the same day as compared to 5.7% in the open thyroidectomy cohort (P = 0.006). Overall rates of complication were comparable (P = 0.65). Transient recurrent laryngeal nerve palsy occurred in 4.6% of patients, which was similar between both cohorts (P = 0.66). CONCLUSION: Robotic completion thyroidectomy appears safe and effective, achieving shorter hospitalization than conventional open approaches despite longer operative times. Appropriate patient selection and surgical technique optimization are key. Larger prospective studies should investigate costs and long-term patient-reported outcomes.

Awareness and Interest in Rhinoplasty and Its Postoperative Complications Among Females in the Northern Border Region, Saudi Arabia.

BACKGROUND: Rhinoplasty is a popular cosmetic surgical procedure that aims to reshape the nose, enhance its appearance, and improve nasal function. This study investigated the awareness, attitudes, and interest in rhinoplasty among females in the Northern Border Region of Saudi Arabia, as well as their knowledge of potential postoperative complications. METHODS: An online survey was used to perform a cross-sectional study. Female participants aged between 18 and 45 years, living in the Northern Border Region of Saudi Arabia, were selected. The questionnaire consisted of three main sections: personal information, attitude toward rhinoplasty, and complications of rhinoplasty. RESULTS: 905 females participated in our study. The majority (87.8%, n=795) had heard about rhinoplasty before, and 54.9% (n=497) knew someone who had undergone the surgery. Social media was the most common source of information about rhinoplasty (67.2%, n=608). A significant proportion of participants (72.4%, n=655) believed that their nose appearance sometimes or always limited their social and professional activities. However, only 16.7% (n=151) expressed a desire to change or improve their nose appearance through surgery. The educational status of the participant (*p*=0.027) and their father (*p*=0.011) were significantly associated with interest in rhinoplasty. Satisfaction with nose appearance, breathing, and family and friends' opinions about the participant's nose were also significantly associated with interest in rhinoplasty (*p*<0.001 for all). The majority of participants (88.4%, n=800) were aware of at least one complication, with the most recognized complications being breath disorders (74.6%, n=675), headache (70.6%, n=639), and mismatch of their new noses with the rest of their faces (69.8%, n=632). Age (*p*=0.008), city of residence (*p*<0.001), and satisfaction of family and friends with the participant's nose (*p*=0.019) were significantly associated with complication awareness. CONCLUSION: This study found that women in Saudi Arabia's Northern Border Region had a high level of awareness and interest in rhinoplasty, despite concerns regarding the safety, availability of educational resources, and ethical considerations in promoting the procedure. The findings highlight the need for accurate and comprehensive information about rhinoplasty and its potential complications to be readily available to the public, particularly through targeted educational interventions and responsible advertising regulations.

Initial versus Staged Thyroidectomy for Differentiated Thyroid Cancer: A Retrospective Multi-Dimensional Cohort Analysis of Effectiveness and Safety.

The optimal surgical approach for differentiated thyroid cancer remains controversial, with debate regarding the comparative risks of upfront total thyroidectomy versus staged completion thyroidectomy following the initial lobectomy. This study aimed to assess the complication rates associated with these two strategies and identify the optimal timing for completion thyroidectomy using a multi-dimensional analysis of four cohorts: an institutional series (n = 148), the National Surgical Quality Improvement Program (NSQIP) database (n = 39,992), the TriNetX repository (n > 30,000), and a pooled literature review (10 studies, n = 6015). Institutional data revealed higher overall complication rates with total thyroidectomy (18.3%) compared to completion thyroidectomy (6.8%), primarily due to increased temporary hypocalcemia (10% vs. 0%, p = 0.004). The NSQIP analysis demonstrated that total thyroidectomy was associated with a 72% increased risk of transient hypocalcemia (p < 0.001) and a 25% increased risk of permanent hypocalcemia (p < 0.001). TriNetX data confirmed these findings and identified obesity and concurrent neck dissection as risk factors for complications. A meta-analysis showed that total thyroidectomy increased the rates of transient (RR = 1.63) and permanent (RR = 1.23) hypocalcemia (p < 0.001). Institutional and TriNetX data suggested that performing completion thyroidectomy between 1 and 6 months after the initial lobectomy minimized permanent complication rates compared to delays beyond 6 months. In conclusion, for differentiated thyroid cancer, total thyroidectomy is associated with higher risks of transient and permanent hypocalcemia compared to staged completion thyroidectomy. However, performing completion thyroidectomy within 1-6 months of the initial lobectomy may mitigate the risk of permanent complications. These findings can inform personalized surgical decision-making for patients with differentiated thyroid cancer.

Technical recommendations for implementation of Volumetric Modulated Arc Therapy and Helical Tomotherapy Total Body Irradiation.

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices.

Risk factors associated with intimate partner violence (IPV) against Jordanian married women: A social ecological perspective.

This paper seeks to gain insights into complex and multiple influences which may behind the different components of intimate partner violence (IPV) against Jordanian wives. Drawing on a quantitative approach, the paper explores and presents findings of the determinants of domestic violence sustained by female partners during the year preceding a nationally representative survey. The survey is based on national multi-stage random sampling data from the 2012 Jordan Demographic Health Survey (JDHS). The paper applies the social-ecological framework. A method of Leastwise deletion techniques is used to remove missing data. Doing this resulted in 6213 married women used in the data analysis. Logistic regression models are used to estimate/predict different forms of IPV against domestic female partners. The findings of the study suggest that wives are victimized at all levels of the framework. Specifically, family, community, and social levels were the most vital factors affecting victims experiencing IPV. More specifically, wives witnessing their fathers beat their mothers and wives who are scared of their husbands are more prone to sustain violence inflicted by their partners. Furthermore, wives' education, working status, and age at marriage do not predict IPV. Another key finding is that wife empowerment in family relationships is a protective factor against domestic violence against her. The implication is that the patriarchal explanation of domestic violence against wives is valid in the Jordanian cultural context. This study underscores the need to reevaluate the effectiveness of Jordan's general human development programs and women empowerment programs as an essential measure for alleviating IPV inflicted on married women in Jordan.

Late presentations and missed opportunities among newly diagnosed HIV patients presenting to a specialty clinic in Lebanon.

Late presentation to medical care of individuals infected with the human immunodeficiency virus (HIV) is linked to poor outcomes and increased morbidity and mortality. Missed opportunities for a prompt diagnosis are frequently reported among late presenters. We aimed to estimate the proportion of late presenters and missed opportunities in diagnosis among newly diagnosed HIV-positive subjects presenting to a specialty clinic in Lebanon. This is a retrospective chart review of all newly diagnosed adult HIV-positive subjects presenting to clinic from 2012 to 2022. Demographic, laboratory, and clinical data were collected at initial HIV diagnosis or presentation to medical care. We defined late presentation as having a CD4 count < 350 or AIDS-defining event regardless of CD4 count. Advanced disease is defined as having a CD4 count below 200 cells/µL or the presence of an AIDS-defining illness, regardless of the CD4 count. A missed opportunity was defined as the presence of an indicator condition (IC) that suggests infection with HIV/AIDS during 3 years preceding the actual HIV diagnosis and not followed by a recommendation for HIV testing. The proportions for demographic, epidemiological, and clinical characteristics are calculated by excluding cases with missing information from the denominator. Our cohort included 150 subjects (92.7% males; 63.6% men who have sex with men (MSM); 33.3% heterosexuals; median age 30.5 years at diagnosis). 77 (51.3%) were late presenters and 53 (35.3% of all subjects, 68.8% of late presenters) had advanced HIV on presentation. Up to 76.5% of late presenters had a presentation with an HIV-related condition at a healthcare provider without getting HIV test within the previous 3 years. The most frequent ICs were weight loss, generalized lymphadenopathy, constitutional symptoms, and chronic idiopathic diarrhea. Overall mortality rate was 4% (6/150 individuals). All-cause mortality among those who presented with AIDS was 15.4% (6/39 subjects). In our setting, late presentations and missed opportunities for HIV diagnosis are common. In the Middle East, AIDS mortality remains high with a large gap in HIV testing. To effectively influence policies, comprehensive analyses should focus on estimating the preventable health and financial burdens of late HIV presentations. Another concern pertains to healthcare providers' attitudes and competencies.

Diagnostic utility of RAS mutation testing for refining cytologically indeterminate thyroid nodules.

RAS mutations are prevalent in indeterminate thyroid nodules, but their association with malignancy risk and utility for diagnosis remains unclear. We performed a systematic review and meta-analysis to establish the clinical value of RAS mutation testing for cytologically indeterminate thyroid nodules. PubMed and Embase were systematically searched for relevant studies. Thirty studies comprising 13,328 nodules met the inclusion criteria. Random effects meta-analysis synthesized pooled estimates of RAS mutation rates, risk of malignancy with RAS positivity, and histologic subtype outcomes. The pooled mutation rate was 31 % (95 % CI 19-44 %) among 5,307 indeterminate nodules. NRAS mutations predominated at 67 % compared to HRAS (24 %) and KRAS (12 %). The malignancy rate with RAS mutations was 58 % (95 %CI=48-68 %). RAS positivity increased malignancy risk 1.7-fold (RR 1.68, 95 %CI=1.21-2.34, p=0.002), with significant between-study heterogeneity (I2=89 %). Excluding one outlier study increased the relative risk to 1.75 (95 %CI=1.54-1.98) and I2 to 14 %. Funnel plot asymmetry and Egger's test (p=0.03) indicated potential publication bias. Among RAS-positive malignant nodules, 38.6 % were follicular variant papillary carcinoma, 34.1 % classical variant, and 23.2 % follicular carcinoma. No statistically significant difference in the odds of harboring RAS mutation was found between subtypes. In conclusion, RAS mutation testing demonstrates clinical utility for refining the diagnosis of cytologically indeterminate thyroid nodules. Positivity confers a 1.7-fold increased malignancy risk, supporting use for personalized decision-making regarding surgery vs. monitoring. Follicular variant papillary carcinoma constitutes the most common RAS-positive malignant histological subtype. See also the graphical abstract(Fig. 1).

Improving the modelling of a multi-leaf collimator with tilted leaf sides used in radiotherapy.

Background and purpose: Multi-leaf collimators (MLCs) with tilted leaf sides have a complex transmission behaviour that is not easily matched by radiotherapy treatment planning systems (TPSs). We sought to develop an MLC model that can accurately match test fields and clinically relevant plans at different centres. Materials and methods: Two new MLC models were developed and evaluated within a research version of a commercial TPS. Prototype I used adjusted-constant transmissions and Prototype II used variable transmissions at the tongue-and-groove and leaf-tip regions. Three different centres evaluated these prototypes for a tilted MLC and compared them with their initial MLC model using test fields and patient-specific quality-assurance measurements of clinically relevant plans. For the latter, gamma passing rates (GPR) at 2 %/2mm were recorded. Results: For the prototypes the same set of MLC parameters could be used at all centres, with only a slight adjustment of the offset parameter. For centres A and C, average GPR were >95 % and within 0.5 % GPR difference between the standard, and prototype models. In center B, prototypes I and II improved the agreement in clinically relevant plans, with an increase in GPR of 2.3 % ± 0.8 % and 3.0 ± 0.8 %, respectively. Conclusions: The prototype MLC models were either similar or superior to the initial MLC model, and simpler to configure because fewer trade-offs were required. Prototype I performed comparably to the more sophisticated Prototype II and its configuration can be easily standardized, which can be useful to reduce variability and improve safety in clinical practice.

Clinical outcomes and tumor microenvironment response to radiofrequency ablation therapy: a systematic review and meta-analysis.

Background: Radiofrequency ablation (RFA) utilizes minimally invasive high-energy current to precisely ablate tumor cells. It has been utilized in many cancer types including thyroid, lung, and liver cancer. It has been shown to provide adequate ablative margins with minimal complications; however, incomplete RFA may lead to recurrence of tumor. The underlying cellular mechanism and behavior of ablated cancer tissue is poorly understood. Methods: A systematic review was performed, searching EMBASE, Web of Science, PubMed, and Scopus for studies published up to March 2022 and reported following PRISMA guidelines. Collection was performed by two groups of investigators to avoid risk of bias. The Cochrane Collaboration's tool was used for assessing risk of bias. We identified human, in vivo, and in vitro research studies utilizing RFA for tumor tissues. We required that the studies included at least one of the following: complications, recurrence, or survival, and took interest to studies identifying cellular signaling pathway patterns after RFA. Descriptive statistical analysis was performed in 'R' software including mean and confidence interval. Results: The most frequent cancers studied were liver and lung cancers accounting for 57.4% (N=995) and 15.4% (N=267), followed by esophageal (N=190) and breast cancer (N=134). The most common reported complications were bleeding (19%) and post-operative pain (14%). In our literature search, four independent studies showed upregulation and activation of the VEGF pathway following RFA, four showed upregulation and activation of the AKT pathway following RFA, three studies demonstrated involvement of matrix metalloproteinases, and four showed upregulation of c-Met protein following RFA. Conclusions: In our review and meta-analysis, we identify several proteins and pathways of interest of which are important in wound healing, angiogenesis, and cellular growth and survival. These proteins and pathways of interest may implicate areas of research towards RFA resistance and cancer recurrence.

Assessing Adequacy: A Meta-Analysis of Rapid Onsite Evaluation of Thyroid Nodules.

INTRODUCTION: Fine-needle aspiration (FNA) is the standard form of preoperative evaluation of thyroid nodule cytological status. A significant number FNAs are classified as inadequate for interpretation, requiring a repeat FNA which is potentially avoidable, costly, and delays treatment. To address these concerns and maximize first-time FNA adequacy, rapid onsite evaluation (ROSE) of FNA specimens was introduced. Our study aims to determine the impact of ROSE on FNA adequacy. METHODS: PubMed, Embase, and Web of Science were searched for primary articles assessing the adequacy of ROSE in thyroid nodules. RESULTS: A total of 17 studies were included for a total of 24,649 thyroid nodes. Thirteen thousand two hundred fifteen (53.6%) thyroid nodules were assessed utilizing ROSE and 11,434 (46.4%) were not. Pooled adequacy increased significantly from 76% without ROSE to 92% with rose (P = 0.001). Use of ROSE increased the odds of adequate FNA by 22% (risk ratio (RR) = 1.22, 95% confidence interval (CI) = 1.12-1.32). At institutions with less than 85% effective diagnostic adequacy without ROSE, the risk for diagnostic adequacy increased by 28% with ROSE implementation (RR = 1.28, 95% CI = 1.20-1.37). In contrast, in studies reported from institutions with an effective diagnostic rate greater than 85% without the use of ROSE, the diagnostic adequacy only increased by 5% with ROSE implementation (RR = 1.05, 95% CI = 1.03-1.06). CONCLUSIONS: The use of ROSE during first-time FNA of thyroid nodules can significantly improve adequacy, especially at institutions with baseline high inadequacy rates. Implementation of ROSE can reduce repeat FNAs and its associated consequences.