Disease and Health Research: Recent Developments Vol. 3

Diabetes-Related Foot Ulceration: A Critical Narrative Review of Pathophysiological Mechanisms, Therapeutic Evidence and Preventive Strategy

S. Shoba — 2026-09-30

Foot ulceration remains the most common cause of hospitalisation and non-traumatic lower-limb amputation among people living with diabetes mellitus, and its five-year mortality approaches that of several common malignancies. Despite three decades of international guideline development and a large therapeutic literature, amputation rates have not fallen consistently, and inequalities in outcome appear to be widening. This critical narrative review examines the state of knowledge on the pathophysiology, assessment, management and prevention of diabetes-related foot ulceration, and asks why an apparently well-characterised causal pathway has proved so resistant to translation into reliable clinical benefit. Literature was identified through structured searching of PubMed, PubMed Central and Europe PMC, the Directory of Open Access Journals, Crossref, Semantic Scholar and Google Scholar, supplemented by backward and forward citation tracking and by examination of guideline evidence syntheses. Sources were appraised for design adequacy, risk of bias, outcome relevance, generalisability and consistency with the wider evidence, and were synthesised thematically rather than sequentially. Three findings dominate the appraisal. First, the classical triad of neuropathy, deformity and trauma is well supported for ulcer initiation, but the relative contribution of arterial disease, medial arterial calcification and microvascular dysfunction to non-healing remains poorly quantified, and mechanistic plausibility has repeatedly outrun demonstrated effectiveness. Second, the interventions with the most secure evidence are mechanical and organisational rather than biological, whereas the largest volume of trial activity concerns advanced wound products supported predominantly by small, industry-sponsored studies of low certainty. Third, prevention rests on a narrow evidential base in which only a few interventions reach moderate certainty, and screening has never satisfied established criteria for population-wide programmes. Heterogeneous outcome definitions, exclusion of ischaemic and infected ulcers from pivotal trials, and marked geographical concentration of research constrain confidence throughout. Priorities include pragmatic trials in unselected populations, standardised outcome reporting, and implementation research addressing the persistent gap between guideline recommendation and delivered care.

Non-Alcoholic Fatty Liver Disease: Pathophysiology, Diagnosis, Current Management, and Future Directions

V. Jenila Jose Jancy — 2026-09-30

Non-alcoholic fatty liver disease (NAFLD), now largely encompassed by metabolic dysfunction-associated steatotic liver disease (MASLD), is a heterogeneous disorder in which common cardiometabolic exposures interact with genetic susceptibility, hepatocellular stress and tissue repair responses. This critical narrative review integrates historical NAFLD evidence with the contemporary MASLD framework and evaluates advances in pathophysiology, diagnosis, risk stratification and treatment through 5 July 2026. Literature was identified through live searches of major open scholarly sources, citation chaining and verification of relevant practice guidance and regulatory information. The evidence supports a shift from a steatosis-centred concept towards fibrosis-centred prognosis and phenotype-specific management. Insulin resistance, excess fatty-acid delivery, de novo lipogenesis, lipotoxicity, organelle stress, inflammatory signalling and hepatic stellate-cell activation form interacting rather than strictly sequential pathogenic processes; genetic variants and gut-liver signalling further modify risk, but neither currently supports routine precision treatment. For diagnosis, single tests are insufficient. Sequential non-invasive assessment, typically beginning with a simple blood-based fibrosis score and escalating to elastography or specialised biomarkers, offers a pragmatic strategy for identifying advanced fibrosis while limiting liver biopsy. Lifestyle intervention remains foundational, with weight reduction and exercise improving steatosis and, when sufficiently sustained, histological activity; long-term implementation is the principal limitation. The therapeutic landscape has changed materially: resmetirom and semaglutide provide disease-directed options for selected adults with non-cirrhotic MASH and F2-F3 fibrosis in the United States, whereas several incretin, pan-PPAR and fibroblast growth factor 21 programmes remain investigational. Important uncertainties persist regarding hard clinical outcomes, optimal treatment sequencing and combination, non-invasive monitoring of response, cirrhosis, lean phenotypes, paediatric disease, long-term safety and equitable access. The strongest current strategy is therefore integrated: identify patients at meaningful fibrosis risk, treat cardiometabolic drivers intensively, deploy disease-directed therapy selectively, and avoid assuming that short-term histological improvement is equivalent to prevention of decompensation, cancer or death.

Emphysematous Pyelonephritis: A Critical Narrative Review of Classification, Risk Stratification and the Evolving Management Paradigm

R. Ghasni Pasil — 2026-09-30

Emphysematous pyelonephritis is a rare but life-threatening necrotising infection of the renal parenchyma and surrounding tissues, defined by the presence of gas within the collecting system, parenchyma or perinephric space. The condition occurs predominantly, although not exclusively, in patients with poorly controlled diabetes mellitus and carries a mortality that historically approached one-half of affected individuals before the modern era of early imaging, intensive supportive care and minimally invasive drainage. This review synthesises the accessible peer-reviewed literature on the classification, pathogenesis, risk stratification and management of emphysematous pyelonephritis, with particular attention to unresolved methodological and clinical controversies rather than a simple restatement of case volumes. The evidence indicates convergence around several points: computed tomography-based classification, whether the two-tier Wan system or the four-tier Huang-Tseng system, correlates broadly with prognosis; thrombocytopenia, altered consciousness, bilateral disease and shock are consistently associated with mortality across independently conducted cohorts; and a conservative-first strategy combining broad-spectrum antimicrobial therapy with percutaneous drainage has progressively displaced emergency nephrectomy as first-line management, with nephrectomy now reserved for refractory or fulminant presentations. Considerable inconsistency nevertheless persists regarding the comparative performance of the numerous prognostic scoring systems proposed over the past two decades, the true independent contribution of diabetes to mortality once confounders are accounted for, and the applicability of predominantly single-centre, retrospective evidence to varied health-system settings. Regional data, particularly from South and East Asia, illustrate both the disproportionate burden of the disease in populations with a high prevalence of diabetes and the persistent underrepresentation of such settings in pooled analyses. This review concludes that while the broad therapeutic direction of travel is reasonably well supported, the evidence base remains constrained by heterogeneous outcome definitions, retrospective design and the near-total absence of prospective comparative trials, leaving several clinically consequential questions without a definitive answer.

Impacted Maxillary Canines: Diagnosis, Treatment and Prognosis Illustrated by a Challenging Clinical Case

Carmen López-Carriches — 2026-09-30

Impacted maxillary canines are an important eruption disturbance requiring coordinated diagnostic, orthodontic, surgical, and periodontal management. This manuscript reviews the epidemiology, aetiology, pathogenesis, diagnosis, treatment options, prognosis, and complications of maxillary canine impaction and illustrates these principles through a challenging clinical case. An 8-year, 10-month-old male patient presented with marked dental crowding and abnormal eruption pathways of both maxillary canines. Interceptive management included maxillary expansion, extraction of selected primary teeth, and subsequent orthodontic space creation. Tooth 13 showed favourable spontaneous progression, whereas tooth 23 remained deeply impacted in a high, almost horizontal buccal position. Cone-beam computed tomography defined the three-dimensional position of tooth 23 and showed no detectable resorption of adjacent roots. Given the patient's young age, incomplete root development, available space, and absence of adjacent root damage, preservation of the permanent canine was attempted using closed surgical exposure followed by controlled orthodontic traction. Serial clinical and radiographic assessments demonstrated progressive inferior movement and improved angulation. By April 2025, the crown had emerged into the oral cavity; by June–July 2026, the canine had been incorporated into the maxillary arch and was undergoing final positioning. The case demonstrates the value of three-dimensional assessment, appropriate surgical selection, controlled biomechanics, and periodontal management in the conservative treatment of a severely displaced maxillary canine.