Autonomic Nervous System Dysregulation in Metabolic Syndrome: An Association With Hypertension and Cardiovascular Risk (2025)

Type of publication:

Systematic Review

Author(s):

Soomra, Hoor; Mukhtar, Asad; *Asif, Fatima; Khalid, Ayesha; Noureen, Sadia; Qamar, Zeeshan; Haider, Usman.

Citation:

Cureus. 17(12):e98932, 2025 Dec.

Abstract:

Metabolic syndrome (MetS) is a cluster of cardiometabolic abnormalities, including abdominal obesity, insulin resistance, dyslipidemia, and elevated blood pressure, that increases the risk of type 2 diabetes and cardiovascular disease (CVD). Autonomic imbalance, characterized by increased sympathetic activity and reduced parasympathetic tone, is proposed to play an important role in the development of hypertension and adverse cardiovascular outcomes in individuals with MetS. This systematic review evaluates the association between autonomic nervous system (ANS) dysregulation and MetS. A systematic search was conducted in PubMed, Embase, Scopus, and Cochrane Library for studies published from January 2015 to September 2025. Eligible studies included human research that examined measures of autonomic function such as heart rate variability (HRV), baroreflex sensitivity, muscle sympathetic nerve activity, and plasma catecholamine levels at rest in individuals with MetS. Observational and interventional studies were included. Data were extracted and synthesized narratively. A total of 16 studies met the inclusion criteria. Most included studies reported reduced HRV, impaired baroreflex sensitivity, increased resting sympathetic nerve activity, and elevated plasma catecholamines in participants with MetS, suggesting a consistent association between ANS dysregulation and blood pressure elevation. However, causality could not be established due to the predominantly observational study designs. Current evidence indicates a significant association between autonomic dysfunction and MetS, particularly in relation to hypertension and increased cardiovascular risk. ANS biomarkers may support refined cardiometabolic risk stratification, although further prospective and mechanistic studies are needed to clarify causal pathways.

DOI: 10.7759/cureus.98932

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Checkpoint Inhibitors and Beyond: A Systematic Review of Immunotherapy in Cutaneous Malignancies (2025)

Type of publication:

Systematic Review

Author(s):

Rashid, Yasir; Devi S, Kartika; Gonzalez-Espinosa, Tomas Faustino; Jain, Juhi; Dalain, Mujahed; Baig, Rayyan; D'Amico, Giuseppe Antonio; Mowo-Wale, Adetola G; Khomchenko, Mariia; Baby, Nima; *Yateem, Dana; Duhamel, Axel; Ali, Ramsha.

Citation:

Cureus. 17(12):e98959, 2025 Dec.

Abstract:

Skin cancers represent a major health concern, and there is a need for more effective treatment approaches, among which immune checkpoint inhibitors have become a particularly important recent development. This study aimed to explore the efficacy and tolerability of immune checkpoint inhibitors, intratumoral immunotherapies, targeted agents, and their combinations in advanced cutaneous malignancies. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-conform review of PubMed (2012-2024) identified 26 studies, including randomized trials, observational cohorts, network meta-analyses, and systematic reviews, evaluating checkpoint inhibitors, anti-PD-1/PD-L1and anti-CTLA-4. Outcomes included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), biomarkers, and treatment-related adverse events. This meta-analysis of 26 studies (2012-2024) evaluated treatments for cutaneous malignancies, including melanoma, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), covering systemic immunotherapies (PD-1, CTLA-4), combination checkpoint inhibitors, and novel approaches like IL-12 electroporation. Melanoma: PD-1 therapies showed durable benefits; ipilimumab retreatment yielded 42% two-year survival. MCC: Avelumab achieved a median OS of 12.9 months. cSCC: Nivolumab PFS 8.2 months; cemiplimab 12-month PFS >53%. Targeted therapy: BRAF/MEK inhibitors reached OS ~33 months. Emerging strategies: TIL-based and neoadjuvant immunotherapy showed high pathological and durable responses. Overall, combination therapies consistently outperformed monotherapies in survival and response. Adverse events were common, especially with combination therapy, with severe immune-related toxicities reported in 30-59% of cases, while monotherapies were generally safer. Overall, immunotherapy offers substantial, often long-lasting benefits, though careful patient selection and monitoring are essential to balance efficacy and toxicity. Combination immunotherapies and targeted regimens are more effective for advanced melanoma, although they have increased toxicity.

DOI: 10.7759/cureus.98959

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Short-Term Functional Outcomes in Patients Undergoing Primary Total Knee Arthroplasty According to Their Body Mass Index (2026)

Type of publication:

Journal article

Author(s):

Bhakar, Ranj; Chakrapani, Arjun S; Shaik, Arfaz; Alexander, Aaron; *Murugesan, Thivagar; Anbazhagan, Prasanna Kumar; Ghent, Dan.

Citation:

Cureus. 18(1):e101269, 2026 Jan.

Abstract:

OBJECTIVE: This study aimed to evaluate the association between body mass index (BMI) and short-term outcomes following primary unilateral total knee arthroplasty (TKA), including functional improvement, perioperative variables, and postoperative complications.

METHODOLOGY: A retrospective case-control study was conducted at a tertiary orthopedic center on 525 consecutive patients who underwent primary unilateral TKA for osteoarthritis between January 2019 and December 2023. Patients were classified according to World Health Organization (WHO) BMI criteria: normal (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (>=30.0 kg/m2). Collected data included demographics, American Society of Anesthesiologists (ASA) grade, Charlson Comorbidity Index (CCI), glycated hemoglobin (HbA1c), operative time, length of hospital stay, change in Knee Society Score (DELTAKSS) at 12 months, patient-reported outcome measures, satisfaction, revision surgery, and postoperative complications. Between-group comparisons were performed using one-way analysis of variance (ANOVA) for continuous variables and chi-square or Fisher's exact tests for categorical variables, with significance set at p < 0.05.

RESULTS: Baseline characteristics were comparable across BMI groups, except for higher ASA scores and HbA1c levels in obese patients (p < 0.05). Obese patients had significantly longer operative times (95.9 +/- 16.8 minutes) and hospital stays (4.8 +/- 1.2 days) than normal-weight patients (83.6 +/- 14.1 minutes; 3.9 +/- 1.0 days, p < 0.01). All BMI groups demonstrated significant improvement in DELTAKSS at 12 months, although the gain was lowest in obese patients (34.7 +/- 10.5 vs. 41.2 +/- 9.6; p = 0.012). Overall complications were highest in the obese group with 16 patients (9.1%), followed by nine patients (5.1%) in the overweight group and seven patients (4.0%) in the normal-weight group, with wound-related issues being the most common. Revision surgery occurred in one (0.6%) obese patient, and no mortality was reported.

CONCLUSION: Higher BMI was associated with longer operative times, prolonged hospital stays, increased wound complications, and slightly reduced functional improvement and satisfaction at 12 months after primary TKA. These findings highlight the importance of optimizing metabolic status before surgery and emphasize the need for individualized perioperative risk assessment in patients undergoing knee arthroplasty.

DOI: 10.7759/cureus.101269

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Is robotic surgery ready for emergency cholecystectomy? A systematic review and meta-analysis of robotic versus laparoscopic approach in acute cholecystitis (2026)

Type of publication:

Systematic Review

Author(s):

Jamal, Zohaib; Talal, Muhammad Anza; Saeed, Jahanzaib; Siddiqui, Asher; Haider, Muhammad Ijlal; Zafar, Khizra; Zaidi, Hammad.

Citation:

Journal of Robotic Surgery. 20(1):166, 2026 Jan 12.

Abstract:

INTRODUCTION: Acute cholecystitis is typically managed with laparoscopic cholecystectomy, though inflammation and distorted anatomy can increase operative difficulty. Robotic cholecystectomy may offer technical advantages through improved visualisation and instrument dexterity, yet current evidence is limited, heterogeneous, and entirely observational, with no randomized trials comparing the two approaches in the emergency setting. This systematic review and meta-analysis synthesises existing comparative data to determine whether robotic assistance confers meaningful operative or postoperative benefits over standard laparoscopy in acute cholecystitis.

MATERIALS AND METHODS: A PRISMA-compliant systematic review and meta-analysis was performed. Comprehensive searches of major databases (2015-2025) identified comparative studies of robotic versus laparoscopic cholecystectomy for acute/emergency cholecystitis in adults. Eligible studies reported at least one perioperative or postoperative outcome; elective, paediatric, single-incision, and non-comparative designs were excluded. Outcomes included operative time, conversion, intra-operative complications, bile duct injury, length of stay, readmission, reoperation, and mortality. Risk of bias was assessed using ROBINS-I. Meta-analyses were conducted in RevMan using random-effects models, with heterogeneity assessed by I2 and standard continuity corrections applied for zero-event studies.

RESULTS: Seven observational studies comprising 143,717 patients met the inclusion criteria. Operative time and length of stay could not be meta-analysed due to inconsistent reporting and were therefore summarised narratively, with both outcomes appearing broadly comparable between robotic and laparoscopic groups. Meta-analysis demonstrated a significantly lower risk of conversion to open surgery with robotic cholecystectomy (RR 0.61, 95% CI 0.50-0.75; I2 = 44%). No significant differences were observed between robotic and laparoscopic approaches for intra-operative complications (RR 0.72, 95% CI 0.38-1.36; I2 = 40%), bile duct injury (RR 0.97, 95% CI 0.77-1.21; I2 = 0%), overall postoperative complications (RR 1.10, 95% CI 0.80-1.52; I2 = 95%), 30-day readmission (RR 0.88, 95% CI 0.50-1.54; I2 = 18%), reintervention or return to theatre (RR 0.33, 95% CI 0.04-2.48; I2 = 78%), or 30-day mortality (OR 1.28, 95% CI 0.86-1.90; I2 = 0%). Event rates for bile duct injury, major complications, reintervention, and mortality were uniformly low across all cohorts, limiting the precision of pooled estimates. Risk-of-bias assessment using ROBINS-I indicated a moderate to serious overall risk of bias in six of the seven studies, primarily due to residual confounding, non-random treatment allocation, and incomplete reporting of disease severity and operative complexity.

CONCLUSION: Robotic cholecystectomy is a safe and feasible alternative to laparoscopy for acute cholecystitis, demonstrating a consistent reduction in conversion to open surgery and comparable intra-operative and postoperative safety outcomes. However, as current evidence is limited to heterogeneous observational studies with incomplete clinical detail, robust prospective research-with detailed severity grading, surgeon-experience assessment, workflow evaluation, and cost-effectiveness analysis-is needed to more clearly define its role in emergency biliary surgery.

DOI: 10.1007/s11701-026-03145-7

Vascular Eagle's syndrome: difficult diagnosis in patient with recurrent transient ischaemic attack. (2026)

Type of publication:

Journal article

Author(s):

Lyons, T; *Saunders, T; Littleton, E; Monksfield, P; Tiwari, A.

Citation:

Annals of the Royal College of Surgeons of England. 2026 Jan 12.

Abstract:

Eagle's syndrome describes the elongation of the styloid process. The condition has been recognised for over 90 years and causes a wide range of symptoms depending on the level of compression. Compression of the internal carotid artery by the styloid process is referred to in the literature as 'stylocarotid syndrome' or 'vascular Eagle's syndrome' (VES), presenting most commonly as arterial dissection and cerebrovascular events. We present the case of a 53-year-old patient who presented with multiple cerebrovascular events over a six-month period. Computed tomography angiography (CTA) suggested VES; however, magnetic resonance imaging (MRI) of the neck revealed no arterial wall abnormalities, including dissection. Despite the escalation of medical therapy, the patient continued to experience multiple transient ischaemic attacks. Following multidisciplinary team discussion and exclusion of other sources of emboli, a transcervical styloidectomy was performed freeing compression of the carotid artery, resulting in the complete resolution of symptoms. VES should be considered in patients with recurrent or unexplained cerebrovascular or cervical neurogenic symptoms even in the absence of arterial injury. We recommend early styloidectomy when there is a strong clinical suspicion of VES to achieve definitive symptom resolution.

DOI: 10.1308/rcsann.2025.0113

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Big tooth, Big problems? (2025)

Type of publication:

Conference abstract

Author(s):

*Shargill I.

Citation:

Journal of the World Federation of Orthodontists. Conference: 10th International Orthodontic Congress. Rio de Janeiro Brazil. 14(6) (pp 479), 2025. Date of Publication: 01 Dec 2025.

Abstract:

Background Patients that present with a macrodont can require complicated treatment. Case summary: A 14 year old patient presented with Class II division 1 incisors on class I skeletal pattern with normal FMPA complicated by a macrodont lower incisor and impacted lower second premolar teeth. Management of macrodontic teeth can be very difficult to manage as they can be unsightly and dealing with space can be difficult to manage whether this is restorative or space closure. Conclusion(s): This case report illustrates that in the patients presenting with macrodontic teeth they can be treated with orthodontics without the complications of long-term restorative implications.

DOI: 10.1016/j.ejwf.2025.07.243

An audit of testosterone referrals to the menopause clinic (2024)

Type of publication:

Conference abstract

Author(s):

*Clark M.; *Magar C.P.; *Ritchie J.

Citation:

Post Reproductive Health. Conference: 33rd British Menopause Society Annual Scientific Conference, BMS 2024. Kenilworth United Kingdom. 30(1 Supplement) (pp 12S), 2024. Date of Publication: 01 Sep 2024.

Abstract:

Objective: Referrals to the menopause clinic for testosterone and low libido have steadily increased. Locally, we have written prescribing information for primary care to follow, after testosterone initiation in the menopause clinic. This prescribing information adheres to British Menopause Society (BMS) guidelines but has only recently been introduced. The objective of this audit was to determine if the BMS guidelines are currently being followed. Method(s): Retrospective case note review of a selection referrals to the Menopause by two speciality registrars training in Menopause. The electronic patient records were reviewed using pre-determined criteria and recorded on the same secure spreadsheet. Result(s): A total of 245 patient notes were reviewed, of these patients 35 had been specifically referred to request testosterone. 33 of these 35 patients were able to fully discuss testosterone in the menopause clinic. All patients were already taking Hormone replacement therapy (HRT). 32 patients reported that their libido had changed around the time of the menopause. Only 15 patients were already taking vaginal estrogen. 6 patients did not have a baseline testosterone level prior to commencement of testosterone. 24 patients were subsequently started on testosterone. Only 10 patients had reported testosterone levels at 3 months. 4 were referred for psychosexual counselling. Conclusion(s): This audit demonstrated how locally we would benefit from keeping a specific log of patients on testosterone. This is to ensure that patients have their baseline testosterone levels and subsequent monitoring, to make sure testosterone levels are being kept in the physiological range. Our audit showed only a small proportion of patients were already using vaginal estrogen, Vaginal dryness can be a contributing factor to low libido. By increasing uptake in vaginal estrogen this may help some patients prior to their referral or potentially reduce the need for referral. In addition, psychosexual counselling was provided for some of these patients and identified further contributing factors towards low libido, highlighting the importance of a holistic approach to the management of low libido. In those where testosterone was not commenced, this was mostly due to low estrogen levels therefore HRT regimes were altered to optimise absorption prior to considering testosterone.

DOI: 10.1177/20533691241273937

Multidisciplinary team stakeholder event driving development of a novel Haemolytic Disease of the Fetus and Newborn (HDFN) national database for improving clinical outcomes of pregnancy affected by alloimmunisation (2024)

Type of publication:

Conference abstract

Author(s):

Wilkes N.; Jeffs B.; Morton S.; Rogers L.; *Shields J.; Graham S.; Young B.; Asquith B.; O'Shea M.; McBride C.; Wilkes C.; Hazell M.

Citation:

Transfusion Medicine. Conference: 41st Annual Scientific Meeting of the British Blood Transfusion Society. Glasgow United Kingdom. 34(Supplement) (pp 37-38), 2024. Date of Publication: 01 Sep 2024.

Abstract:

Introduction: HDFN is caused by incompatibility between maternal and fetal red cells, stimulating maternal antibody formation and attacking antigen positive fetal red cells, causing haemolysis (Poole and Daniels, 2007). Severity ranges from mild symptoms of jaundice & anaemia to fatal haemolysis (RCOG, 2014). Scientific advances including anti-D prophylaxis and fetal genotyping have improved clinical care and reduced the occurrence of HDFN (BSH, 2016). Guidelines recommend regularly monitoring maternal blood samples during pregnancy to determine antibody formation and titration, identifying any potential risk to the fetus, thus informing clinical decisions and intervention (BSH, 2016). Reviewing guidelines through evidence base analysis is best for patients, ensuring appropriate management plans. NHSBT historically collected data on outcomes of pregnancies with clinically significant alloantibodies. This project aims to launch a novel data collection platform populating a national pregnancy outcomes database ensuring best practice, prevention and treatment in HDFN. Stakeholder engagement and collaboration is essential, here we present the insights gained and the next steps. Method(s): Stakeholders were surveyed prior to the event to inform current practice and guide the face-to-face event agenda. Continuous improvement tools (including Kano analysis) were employed to facilitate guided evaluation and re-design of the current questionnaire & novel digital platform needs. Stakeholders were split into groups with various professional backgrounds allowing different perspectives to be sought. Following the event attendees had access to the collaborative whiteboard tool, Miro, to further understand challenges and requirements. Results and Discussion: Stakeholder output was key to redesigning a user-friendly questionnaire and drive development of a novel digital platform to promote national uptake. Multidisciplinary team collaboration of clinical, laboratory and operational colleagues across organisations gained helpful intel enabling patient focussed outcomes. This approach enabled open discussions capturing ideas to frame service development. Utilisation of the Kano model was an insightful way of understanding user requirements. Conclusion(s): The expanding dataset will be used to inform future guidelines by questioning which pregnancies are at higher risk of HDFN. Increased information aids in providing optimal care to mothers and their babies. Usage of large datasets to benefit patient outcomes are key strategic priorities within Transfusion 2024 (Stanworth et al, 2023).

DOI: 10.1111/tme.13084

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Tumour immune microenvironment prognostic factors in locally advanced rectal cancer, a systematic review (2025)

Type of publication:

Journal article

Author(s):

Ball, Alasdair; *Lefroy, Rebecca; Price, Malcolm; McArthur, David; Beggs, Andrew.

Citation:

Frontiers in Oncology. 15:1688696, 2025.

Abstract:

Introduction: Understanding factors influencing individual survival outcomes following surgical resection of locally advanced (LARC) rectal cancer remains challenging. Novel biomarkers could show emerging promise in this setting. This study aimed to systematically review the literature on immune prognostic factors in LARC.

Methods: The review protocol was preregistered on the PROSPERO database (CRD42023460541). Included studies were required to report overall survival and at least one immune prognostic factor for at least ten patients with LARC. Final searches of MEDLINE, EMBASE and Central were concluded on 8th September 2023. The risk of bias was assessed using the QUIPS tool.

Results: 22 retrospective cohort studies involving 2,622 LARC patients were included in the review. We did not find any published data on immune prognostic factors in locally recurrent rectal cancer. Due to inconsistency of immune prognostic factor definitions and measurement methods, meta-analysis would not be meaningful. Instead, the results are presented descriptively. Risk of bias was concentrated in the participation, attrition, and confounding domains. Greater cytotoxic cell infiltration was associated with improved overall survival. There was inconsistent evidence of an association of PD-L1 expression and survival. M2 macrophage infiltration and homozygous germline FPR1 loss-of-function were associated with worse survival.

Discussion: These findings support a role for both innate and acquired immune systems in mediating outcomes following surgery for LARC and suggest that further work into immunomodulation may show promise in improving LARC treatment.

DOI: 10.3389/fonc.2025.1688696

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Artificial Intelligence in Colonoscopy: A Systematic Review of Adenoma Versus Polyp Detection Rates (2025)

Type of publication:

Systematic Review

Author(s):

Rabba, Waseem; *Asif, Fatima; Younis, Muhammad Y; Nasrullah, Haris; Fatima, Laraib; Arif, Muhammad A.

Citation:

Cureus. 17(12):e98528, 2025 Dec.

Abstract:

Colonoscopy is the gold standard in the prevention of colorectal cancer, but the miss rates of adenoma are high, which restricts its efficacy. To improve lesion recognition, artificial intelligence (AI), especially computer-aided detection (CADe) systems, has been introduced. The aim of this systematic review was to compare AI-assisted colonoscopy in terms of its ability to improve adenoma detection rate (ADR) and polyp detection rate (PDR). An extensive search was performed on PubMed, Embase, and Cochrane Library from 2015 to 2025. There were 17 randomized controlled trials (RCTs) comparing the use of AI-assisted colonoscopy with normal colonoscopy. The methodological quality measure of the included RCTs was Cochrane Risk of Bias 2.0 (RoB 2.0), which subdivided the studies based on low risk, some concerns, or high risk of bias based on whether they were biased in this or that domain. The robVis tool was used to produce the visual summaries. AI-aided colonoscopy effectively enhanced both adenoma detection rate (ADR) and polyp detection rate (PDR) in all of the included studies over conventional colonoscopy. In adenoma detection, accuracy was more than 85%, and in polyp detection, more than 90%. The advantage was also found especially in the detection of small and flat adenomas, which are very often missed in routine practice. The use of AI in colonoscopy is strongly associated with an increase in the detection rate of adenoma and polyps, minimizing the risk of underdiagnosis. The results highlight the clinical promise of AI in the form of a decision-support tool across gastroenterologists and suggest that AI can be applied to enhance the outcomes of preventive and screening colorectal cancer. Future research should be cost-efficient and practical, and combined with some clinical activities.

DOI: 10.7759/cureus.98528

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