Medical Science: Updates and Prospects Vol. 4

Shifting the Paradigm: Bruton's Tyrosine Kinase (BTK) Inhibition as a Game Changer in Blood Cancer Therapy

Swati Shaileshkumar Pawar — 2026-01-15

The pathophysiology of Bruton's tyrosine kinase (BTK) in haematological malignancies is characterised by its central role in aberrant BCR signalling that drives malignant B-cell survival, proliferation, and resistance. The discovery and development of BTK inhibitors have revolutionised the therapeutic approach to these diseases by specifically targeting this key molecular node, disrupting the pathological signalling cascades that sustain malignancy. BTK inhibitors can be broadly categorised into covalent and reversible types based on their mode of binding. Covalent inhibitors, such as ibrutinib, form an irreversible bond with the cysteine residue (C481) in the BTK active site. This permanent attachment prevents ATP binding and subsequent kinase activity, leading to durable inhibition of BCR signalling. The clinical success of BTK inhibitors has revolutionised the treatment of haematological malignancies, yet challenges remain that drive ongoing research and innovation. One significant future direction involves the development of next-generation BTK inhibitors designed to overcome resistance and improve safety profiles. Combination therapies have emerged as a crucial strategy to enhance the effectiveness of BTK inhibitors and to overcome mechanisms of resistance. One of the most promising combinations involves pairing BTK inhibitors with BCL-2 inhibitors such as venetoclax.

From PCOS to Acromegaly: Diagnostic Challenges in a Young Female Patient

Manel Jemel Hadiji — 2026-01-15

Background: Hirsutism, though common in women of reproductive age, is classically associated with polycystic ovarian syndrome (PCOS). It is rarely seen as a prominent feature of acromegaly because of its lack of specificity and occurrence. Acromegaly is caused by chronic hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Diagnosis of acromegaly remains a challenge when the patient may have only subtle features of insulin resistance and PCOS in women.

Case Presentation: This study reports a case of a 28-year-old female with a 3-year duration of oligoamenorrhea and hirsutism. She was followed by a gynaecologist who retained the diagnosis of polycystic ovary syndrome (PCOS). After 5 years, the patient complained of increased hand, finger, and shoe size. She was referred to the endocrine department for suspicion of Acromegaly. Clinical examination revealed acromegaloidism features with mandibular prognathism and moderate macroglossia wic. Biological investigations were significant for elevated insulin-like growth factor 1 (IGF-1) level (774 ng/ml, normal: 98-290 ng/ml) and a growth hormone level not suppressed by a glucose challenge test. MRI brain revealed a pituitary macroadenoma (10.7x14 mm). The patient underwent an uncomplicated transsphenoidal resection of a pituitary macroadenoma. Immunohistochemistry demonstrated a GH tumour. The patient subsequently had normalisation of growth hormone dynamics and regular menstrual cycles.

Discussion: The cause of hirsutism in acromegaly is not well known. In acromegaly, chronic elevated growth hormone levels result in elevated total and free IGF-1. Patients with acromegaly are often insulin-resistant due to the insulin-antagonistic effects of elevated circulating growth hormone. GH decreases sex hormone binding globulin levels, which leads to increased free testosterone levels in patients with acromegaly despite normal testosterone levels.

Conclusion: This case highlights the importance of looking out for subtle features of acromegaly in patients with hirsutism and going for hormonal investigation to make the diagnosis of acromegaly at an earlier stage of the disease. Early diagnosis is critical to prevent the long-term morbidity and mortality associated with acromegaly, as it is a potentially life-threatening condition.

Pericarditis as the First Sign of Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Induced by Methimazole: An Uncommon Onset

Manel Jemel — 2026-01-15

Background: Thiamazole (Methimazole) is one of the antithyroid drugs (ATDs) that are the most commonly used as first-line therapy in the treatment of thyrotoxicosis due to Graves’ disease and toxic nodular goitre in Tunisia. Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of rare diseases characterised by autoimmune-associated inflammation and vessel damage. AAV can be induced by ATDs, with PTU being more commonly associated with the condition, though it often remains misdiagnosed. Cardiac involvement, particularly pericardial effusion, is uncommon in these cases.

Case Report: This chapter reports a case of a 25-year-old woman who had a history of Graves’ disease treated by Methimazole (MMI) 20 mg daily for one year. She was admitted because of pericardial effusion. Two days later, necrotic-looking vasculitic skin lesions appeared. Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) was confirmed by serum test and skin biopsy. The MMI was suspected to be the culprit and was immediately withdrawn. She progressively improves her symptoms, and her skin lesions and pericardial effusion were resolved.

Conclusion: Although the association between PTU and AAV is well-documented, less than 1 of 6 ANCA-positive patients treated with ATDs developed AAV. This is the first case report of pericarditis as the first sign of AAV induced by Methimazole. The withdrawal of the offending medication is the fundamental pillar of the therapeutic approach to avoid more severe complications.

Relevance of Screening Subclinical Cushing’s Syndrome in Patients with Type 2 Diabetes Mellitus

Manel Jemel Hadiji — 2026-01-15

Background: Subclinical Cushing’s syndrome (SCS) is characterized by autonomous cortisol secretion in patients devoid of specific clinical symptoms of hypercortisolism, as in the classic CS. This subtle hypercortisolism, often arising from adrenal incidentalomas, leads to alterations in the hypothalamic-pituitary-adrenal (HPA) axis despite the absence of typical clinical features. Despite the absence of overt symptoms, sustained exposure to chronic, slightly elevated cortisol concentrations may result in some classical metabolic complications of CS, such as impaired glucose tolerance and diabetes. Several studies have reported a higher frequency of SCS in type 2 diabetics, which can be considered an exacerbating factor for diabetes and poor glycemic control. Currently, the frequency of SCS is widely variable.

Aim of the Study: This study intends to prospectively evaluate the prevalence of SCS among type 2 diabetic (T2D) patients with poor control, and to determine whether systematic screening for SCS in T2D patients is worthwhile.

Methods: It was a cross-sectional study including 221 T2D patients referred to the National Institute of Nutrition of Tunis for poor glycemic control (HbA1c ≥ 8%). Inclusion criteria were age >40 years and poor glycemic control; patients with a history of adrenal mass or pituitary adenoma were excluded. SCS screening was performed in two steps. The first screening step of SCS was the 1-mg overnight dexamethasone suppression test (ODST) using a revised criterion for cortisol suppression. In the second confirmatory step, patients with abnormal ODST underwent a 48-h, 2-mg low-dose dexamethasone suppression test (LDDST) to confirm the diagnosis. The cut-off for cortisol suppression was 50 nmol/L (1.8 µmol/dL) in the two tests.

Results: The mean age ± SD of the patients was 58.7 ± 8.78 years. Overweight and obesity were found in 34% and 47%, respectively. Mean duration of diabetes was 10.84 ± 6.55 years, and mean baseline HbA1c ± SD was 10.9±1.8%. Thirteen patients (5.9%) failed to suppress cortisol levels less than the cut-off after ODST. SCS was confirmed by LDDST in one patient among them (0.45%). The autonomous cortisol secretion was related to a pituitary adenoma. This study revealed that the frequency of SCS of 0.45% did not allow for performing an analytical study in order to identify predictive factors of SCS among T2D patients.

Conclusion: SCS is rare among T2D patients. Systematic screening of SCS in T2D patients with poor glycemic control is not worthwhile. The screening should be performed only in patients with specific clinical and/or biological indicators. Further multicenter studies with larger sample sizes are needed to explore potential risk factors for SCS in T2D patients.

Clinical Profile and Management of Oral and Maxillofacial Tumours in HIV-Seropositive Patients

O.O Omisakin — 2026-01-15

Background: There has been an increased rate of neoplastic diseases in patients with Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS). The survival of patients with Human Immunodeficiency Virus (HIV) has improved considerably with modern medical management. However, oral and maxillofacial tumours occurring in these patients have not received adequate treatment attention.

Objectives: To assess the clinical features and treatment modalities of oral and maxillofacial tumours in HIV-seropositive patients.

Methodology: This was a retrospective study of HIV-seropositive patients who received treatments for oral and maxillofacial tumours at Barau Dikko Teaching Hospital, Kaduna, Nigeria. The study covered the period from January 2015 to December 2024. The information was extracted from case files of patients, the theatre register, and histopathology records and slides were retrieved for the purpose of the study. Data collected include patient demography, location of tumour, clinical features, histopathology diagnosis, treatment, and complications.

Results: This study identified 28 HIV-positive patients with various oral and maxillofacial tumours. The age range of the patients was from 26 years to 58 years. Mean age was 42 years, SD ±9.24 years. The tumours include: Kaposi sarcoma (KS), non-hodgkin lymphoma, squamous carcinoma of the oral cavity and oropharynx, mucoepidermoid carcinoma of the parotid gland, parotid cyst, who were treated over a period of 10 years with surgery and radiation therapy. Data collected showed that HIV-positive patients with these tumours presented at the third and fourth decades of life, with aggressive disease and worse prognosis. Treatment comprises surgical resection with radiation therapy and chemotherapy. The complications of the treatment include: tumour recurrence, resistance of the tumour to radiotherapy and chemotherapy, rapidity of tumour growth, acute reactions to radiotherapy, distant metastasis, weight loss and death. Highly active antiretroviral therapy (HAART) has not altered the incidence of these malignancies as observed in this study.

Conclusions: Oral and maxillofacial tumours in HIV-positive patients occurred irrespective of the commencement of highly active antiretroviral therapy. Kaposi sarcoma is the most common tumour recorded in this study. The treatment comprises surgery, chemotherapy and radiotherapy; nevertheless, the response varied with the kind of tumours being treated. Infection with HIV is not a contraindication when aggressive radiation therapy is needed in selected patients.

An Update on the Clinical Scoring Systems for Acute Appendicitis: A Review

Kumar H.R. — 2026-01-15

Clinical scoring systems have been employed in the diagnosis of acute appendicitis, demonstrating varying levels of efficacy. The Alvarado scoring system is the most prevalent, followed by other systems such as the RIPASA and AIR systems. These scoring systems are generally effective in excluding appendicitis or identifying patients who may require additional imaging, such as ultrasound or computed tomography. However, clinical scoring systems are not typically used in isolation to diagnose acute appendicitis. This review article has been conducted to examine the commonly utilised scoring systems and assess their sensitivity and specificity. A literature review was conducted using secondary sources. Findings indicate that all the studies scored were good at ruling out acute appendicitis, but they cannot be used on their own to diagnose acute appendicitis. Further investigations, such as imaging with ultrasound or computerised tomography, may be required to diagnose acute appendicitis. Further randomised, prospective studies are required to more comprehensively assess their clinical efficacy.

Recent Advances in the Management of Mirizzi’s Syndrome: A Review

Kumar H.R. — 2026-01-15

Mirizzi's syndrome represents a rare complication of acute cholecystitis, yet it is associated with considerable morbidity. The diagnosis is challenging, with preoperative identification achieved in only 50% of cases due to the non-specific nature of clinical symptoms. Typically, diagnosis is facilitated through endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP), as ultrasound and computed tomography exhibit low sensitivity for this condition. The treatment approach for Mirizzi's syndrome is contingent upon its classification. Grades 1 and 2 necessitate a cholecystectomy, grade 3 requires a subtotal cholecystectomy, and grade 4 may necessitate a hepatic-enterostomy or choledochal-enterostomy. This review article has been conducted to examine the diagnostic and management strategies for Mirizzi's syndrome.

Comparing Metabolic Outcomes Associated with Aripiprazole and Olanzapine in Schizophrenia Spectrum Disorder: Insights from a Large Real-World Cohort Using TriNetX

Cameron Asay — 2026-01-15

Background: Second-generation antipsychotics manage schizophrenia spectrum disorders but carry metabolic risks. Olanzapine is associated with greater metabolic liability, while aripiprazole is considered more metabolically neutral. Although multiple randomised controlled trials and meta-analyses have compared these agents, results have varied depending on duration, dosage, and population characteristics. Also, only a few large-scale real-world studies have examined these associations across diverse populations using harmonised electronic health records.

Aims: This study compares the risk of developing hyperlipidemia, diabetes mellitus, and pancreatitis among adults prescribed aripiprazole versus olanzapine using electronic health record data.

Methods: A retrospective cohort study was performed using the TriNetX Research Network. Adults aged 18-80 years with schizophrenia spectrum disorders (ICD-10: F20-F29) were included. Cohorts consisted of patients prescribed aripiprazole (n=94,759) and patients prescribed olanzapine (n=1,716,356). After 1:1 propensity-score matching by age, sex, race, and ethnicity, each cohort included 94,125 patients. Incidence of the composite metabolic outcome was compared using risk estimates, Kaplan-Meier analysis, log-rank testing, and Cox proportional hazards modelling.

Results: The metabolic outcome occurred in 27.7% of aripiprazole patients and 20.1% of olanzapine patients. Aripiprazole was associated with higher metabolic risk: risk difference 0.076 (95% CI:0.073-0.080; p<0.001), risk ratio 1.380 (95% CI:1.358-1.403), and odds ratio 1.526 (95% CI:1.494-1.559). Kaplan-Meier analysis demonstrated lower event-free survival for aripiprazole (60.87%) versus olanzapine (68.93%) (log-rank χ²= 875.280; p<0.001). The hazard ratio was 1.33 (95% CI:1.300-1.350), and the proportional hazards assumption was met (p=0.791).

Discussion: Patients treated with aripiprazole demonstrated a higher observed incidence of the combined metabolic outcome compared with those receiving olanzapine. These findings are counter to the conventional expectation that olanzapine carries greater metabolic risk, suggesting that the established metabolic advantage of aripiprazole may not always hold in usual clinical practice. This observation may reflect residual confounding, differential monitoring frequency, prescribing bias, and effects of high statistical power rather than a clinically large difference. From a clinical perspective, these results underscore the importance of individualised antipsychotic selection and routine metabolic surveillance regardless of a medication’s perceived safety profile.

Conclusion: In this large real-world analysis, aripiprazole was unexpectedly associated with a higher incidence of metabolic complications than olanzapine, challenging assumptions regarding aripiprazole’s metabolic advantage and highlighting the need for ongoing metabolic monitoring.

Understanding the Circle of Willis: Anatomy and Variations with Clinical Implications

Rajani Singh — 2026-01-15

The human brain is the main controlling organ of the body. So, the normal and varied anatomy of the brain, including its vascular supply, is very important for neurosurgeons for the management of neurovascular diseases of the brain. Now, the brain is supplied by mainly irrigated by the internal carotid artery and basilar-vertebral arteries and branches of these arteries form an arterial polygon known as the circle of Willis at the base of the brain. Standard configuration of the circles of Willis is present in only one-third of the population only emphasising that quite a large population suffers from variation in the formation of the circle of Willis. The main variations of the circle of Willis include asymmetry, fenestration, duplication, aplasia, agenesis, curved, kinked and tortuous course of the arteries forming the circle of Willis. These variations may lead to aneurysm, stroke and may cause ischemia of parts of the brain supplied by arteries forming the circle of Willis. These clinical conditions may be fatal. So, to manage these clinical conditions of the brain, thorough knowledge of the normal and varied anatomy of the circle of Willis is very important for neurosurgeons. The aim of this chapter is to expound the normal anatomy along with the variations associated with the arteries forming the circle of Willis so that vascular diseases of the brain can be managed successfully with minimum complications.

Current Knowledge on the Role of Monocytes and Macrophages in the Pathogenesis of Non-AIDS Defining Events: Mechanisms, Host Factors, and Therapeutic Implications

Samuel Adinoyi Adavba — 2026-01-15

Monocytes and macrophages play a crucial role in the development of HIV infection, contributing not only to viral persistence but also to the development of non-AIDS-defining events (nADEs) in People Living with HIV (PLWH). These innate immune cells serve as long-lived viral reservoirs, driving chronic inflammation through persistent immune activation, oxidative stress, and tissue-specific damage. HIV-infected monocytes infiltrate tissues such as the cardiovascular system, liver, kidneys, and central nervous system, where they differentiate into macrophages and release pro-inflammatory cytokines (e.g., TNF-α, IL-6), reactive oxygen species (ROS), and matrix metalloproteinases (MMPs). These mediators promote endothelial dysfunction, fibrosis, and organ damage, underpinning conditions like atherosclerosis, neurocognitive disorders, and hepatorenal disease. Emerging evidence highlights the importance of macrophage polarisation (M1/M2 imbalance) and epigenetic modifications in sustaining inflammation, even during antiretroviral therapy (ART). Besides persistent immune activation, the ability of these cells to cause tissue-specific damage is significantly influenced by host genetic factors, such as polymorphisms in the APOL1 and CCL2 genes, which can determine the severity of end-organ diseases like HIV-associated nephropathy. Additionally, epigenetic reprogramming of monocytes and macrophages—triggered by HIV proteins and the inflammatory environment—establishes a lasting pro-inflammatory state that remains despite ART. This reprogramming, marked by changes in histone modifications and DNA methylation, sustains mechanisms of tissue damage. Understanding these processes and their interaction with host factors provides critical insights for developing targeted treatments, including immunomodulators, antioxidants, and strategies for reservoir elimination. This review summarises current knowledge on how monocytes and macrophages contribute to the pathogenesis of nADEs. It explores potential new therapeutic approaches to reduce chronic inflammation and enhance clinical outcomes in PLWH.

Radiowave-Assisted Iridocyclectomy for Anterior Uveal Melanoma: A 13-Year Clinical Study

Maletskyy Anatoliy Parfentievic — 2026-01-15

Background: Uveal melanoma is a highly malignant tumour of the eye, which is characterised by melanocytic tumour growth within the uveal tract of the eye. There is a nearly equal distribution of primary uveal melanoma gender. The management options include transpupillary thermotherapy, brachytherapy, stereotactic radiotherapy, limited surgical resection, enucleation and orbital exenteration. Complications in the surgical removal of pre-equatorial tumours are largely technique-related and may be reduced by combining tumour resection with simultaneous vessel coagulation using radiowave surgery.

Purpose: The aim of this study is to determine the efficacy of resecting iris and ciliary body melanoma with the use of a 3.8-4.0-Mhz radiowave surgery unit.

Methods: This study was carried out at the Department of Eye Cancer, the Filatov Institute, between 2005 and 2018 and included 45 patients with iris and ciliary body melanoma, with a mean age of 56.3 ± 2.2 years and a slight predominance of female patients (53.3%). Sixty-seven patients who had undergone iridociliary melanoma excision using a conventional technique with cutting tools were used as retrospective controls. The eye examination included visual acuity measurement, perimetry, biomicroscopy and ophthalmoscopy. Tumour, nodus и metastasis (TNM) staging was according to the American Joint Committee on Cancer (AJCC). No metastases were seen at the time of enrollment. The mean tumour prominence at baseline was 4.0 ± 0.3 mm, with a mean base diameter of 8.3 ± 0.4 mm, corresponding to a tumour volume of 34.3 ± 0.7 mm³. Patients in both groups were stratified by baseline visual acuity into two subgroups (0.1–0.5 and 0.6–0.8). In the study group, subgroup 1A included 37 patients (82.2%) with visual acuity of 0.1–0.5, while subgroup 1B comprised 8 patients (17.8%) with visual acuity of 0.6–0.8, and in the retrospective control group, subgroup 2A consisted of 55 patients (82.1%) with visual acuity of 0.1–0.5, and subgroup 2B included 12 patients (17.9%) with visual acuity of 0.6–0.8 (p > 0.05). The analysis was performed by analysis of variance (ANOVA) using Statistica 13.0 (Dell Statsoft Inc., Austin, TX).

Results: The radiosurgical approach to treatment of iridociliary tumours in our patients allowed significantly reducing the rates of intraoperative and postoperative complications (χ2=4.16; df=1; p=0.04). In addition, the rates of intraoperative and postoperative complications for the treatment of iridociliary tumours with cutting instruments were 9.1% and 10.4%, respectively. The use of a radiowave surgery unit for uveal melanoma resection allowed preserving baseline visual acuity in all patients, with a tumour recurrence rate of not more than 2.2%.

Conclusion: The use of a radiowave surgery unit for uveal melanoma resection allowed preserving baseline visual acuity in all patients. Early (12-month) treatment outcomes (visual functions and postoperative clinical course) and late treatment outcomes (visual functions; optic media; IOP; and tumour recurrence) for iridociliary melanoma resection using a radiowave 3.8-4.0 MHz unit allow us to state that high-frequency radiowave surgery enables reducing the risk of intraoperative and postoperative complications and, consequently, preserving a good visual function.

A Preschooler's Displaced Mandibular Body Fracture: A Closed Reduction Case Study

Mekhaeel Shehata Fakhry Mekhaeel — 2026-01-15

Because developing tooth buds and development centres make treating mandibular fractures in young patients more difficult, conservative approaches are often used to avoid iatrogenic damage. This report describes the application of this approach to a 4-year-old kid who had a displaced left mandibular body fracture after a fall. A CT scan verified that the fracture was successfully treated with closed reduction and maxillomandibular fixation (MMF), which was performed completely intraorally using arch bars and elastics. The 30-minute procedure yielded an excellent outcome with no issues, and the patient's function and appearance were entirely restored after a four-week fixing period. This case study demonstrates that closed reduction with MMF is a highly effective, minimally invasive approach for treating some mandibular fractures in young children while preserving growth potential and ensuring proper healing.

Coexisting Inguinal and Umbilical Hernias as a Clinical Indicator of Diffuse Abdominal Wall Deficiency: A Case Study

Mekhaeel, Shehata Fakhry Mekhaeel — 2026-01-15

The lifetime risk profile for inguinal hernia is characterised by a profound sexual dimorphism, with males facing an approximate 27% cumulative incidence, ninefold greater than the 3% risk observed in females. This condition exhibits a marked predilection for the elderly, where its incidence peaks at roughly 13 cases per 1,000 individuals. Notably, the global epidemiological burden of inguinal hernia has escalated significantly, demonstrating a 36% surge in occurrence over the preceding three decades. In the spectrum of anterior abdominal wall defects, umbilical hernias rank as the third most prevalent, manifesting in an estimated 5% to 12% of the adult population. Against this clinical backdrop, this case report investigates the procedural viability and outcomes of a single-stage surgical strategy for the concomitant management of inguinal and umbilical hernias. We present a 62-year-old male patient with a 12-month history of a symptomatic, reducible right indirect inguinal hernia (4x2x2 cm) and an incidental, reducible umbilical hernia (3x3x2 cm) with exertion-triggered pain. The patient had no significant comorbidities or history of incarceration. He successfully underwent a unified operative session under spinal anaesthesia, comprising a standard Lichtenstein hernioplasty for the inguinal defect and a modified Mayo repair augmented with polypropylene mesh for the umbilical hernia. The total procedural duration was recorded at 80 minutes. The postoperative convalescence was uncomplicated, facilitating discharge on the sixth day. Critically, at the 36-month long-term follow-up, the patient reported complete resolution of symptoms and exhibited an excellent clinical outcome. There was no radiological or clinical evidence of recurrence at either surgical site, nor were there any sequelae of chronic groin pain, mesh-related complications, or surgical site infection. This successful outcome substantiates the proposition that a single-stage, mesh-reinforced repair under spinal anaesthesia constitutes a clinically feasible and resource-optimised therapeutic pathway. The approach offers distinct advantages by consolidating the surgical intervention into a solitary anaesthetic episode and a unified recovery period, thereby enhancing patient convenience and potentially reducing systemic healthcare costs. Nevertheless, while these preliminary results are highly encouraging, they necessitate rigorous corroboration through prospective, randomised controlled trials with larger cohorts. Such studies are imperative to definitively establish this integrated approach as a superior and standard-of-care alternative to traditional staged repairs for suitable patient candidates.