Raphael Figuiredo Dias

Background: Anatomical variants of the cystic duct impair attainment of the critical view of safety during laparoscopic cholecystectomy, predisposing to bile duct injury, bile leak, and conversion to open surgery. No prior synthesis has examined their prevalence across all detection modalities. Objectives: To determine the pooled prevalence of cystic duct anatomical variants and their association with surgical outcomes. Data Sources: MEDLINE/PubMed, Embase, and Cochrane CENTRAL were searched from January 2000 to November 2025. Reference lists were hand‐searched for additional eligible studies. Review Methods: PRISMA 2020‐compliant systematic review and meta‐analysis. Pooled prevalence estimates were calculated using a random‐effects model with Freeman–Tukey double arcsine transformation. Heterogeneity was assessed using the I ² statistic and Cochran's Q test. Quality was assessed using the JBI Prevalence checklist. Prospectively registered: PROSPERO (CRD420251178103). Results: Fifty‐three studies ( n = 18 875 patients; 22 countries) were included. The pooled prevalence of any cystic duct variant was 19.1% (95% CI 13.2%–25.7%). Variant‐specific estimates were: high insertion 16.6% (9.2%–25.6%; k = 16), medial insertion 7.3% (4.0%–11.5%; k = 19), low insertion 6.5% (4.2%–9.2%; k = 29), spiral/posterior course 14.6% (8.2%–22.5%; k = 17), and right hepatic duct insertion 1.3% (0.7%–2.1%; k = 15). Heterogeneity was considerable ( I ² = 79.6%–99.4%), attributable to variation in detection modality and classification systems. Only 11 studies (20.8%) reported surgical outcomes; pooled conversion to open surgery rate was 11.0% (95% CI 6.9%–15.2%). No significant publication bias was detected (Egger's test p = 0.208). Conclusion: Cystic duct anatomical variants affect approximately one in five patients undergoing biliary imaging or cholecystectomy. The lack of a universal system and the paucity of outcome data stratified by variant subtype represent a major gap. Prospective studies using standardised nomenclature and systematically reporting surgical outcomes are urgently needed.

Background: Losing-salt tubulopathies, such as Bartter syndrome, are rare and usually inherited due to mutations of tubular reabsorption channels of the nephrons. Despite its scarcity, some cases of acquired losing-salt tubulopathies have been described. In this case report, we discuss the main aspects of Bartter syndrome and present a rare pediatric case of probable tacrolimusinduced Bartter-like syndrome in a renal transplanted boy. Case Presentation: A ten-year-old male patient with end-stage renal disease due to endo and extra capillary glomerulonephritis was submitted to renal transplantation from a deceased donor. The post-operatory evolution was satisfactory with normalization of serum creatinine levels, mild hypertension, and the absence of metabolic disorders. The immunosuppression protocol included tacrolimus (0.3 mg/kg/day), mycophenolate (455 mg/m2/day) and prednisone (0.5 mg/kg/day). Two months later, the patient was hospitalized due to vomiting, dehydration, intense hypokalemia (1.3 mEq/L), hyponatremia (125 mEq/L), and hypochloremia (84 mmol/L). During hospitalization, he evolved with polydipsia (3000 mL/day) and polyuria (120-160 mL/m2/h) associated with major elevation of urinary potassium excretion, hypercalciuria, mild metabolic alkalosis, hyperfiltration, and proteinuria. The tacrolimus dose was reduced under the suspicion of tubular dysfunction, leading to a better metabolic profile. However, the patient developed a Banff IIb graft rejection, which required pulse therapy and elevation of tacrolimus and mycophenolate doses. Recovery of renal function parameters occurred, but the metabolic disorders worsened following tacrolimus dose elevation. The patient required chronic potassium, chloride, and sodium replacement. Conclusion: After administering immunosuppressive medications, physicians should be aware of the possibility of Bartter-like or other losing-salt tubulopathies syndromes that can affect metabolic homeostasis. The suspicion must always be considered in the case of a transplanted patient who presents dehydration and hydroelectrolytic disorders right after the commencement of nephrotoxic immunosuppressive drugs, including tacrolimus and cyclosporine.

Lupus nephritis (LN) is severe renal comorbidity associated with systemic lupus erythematosus (SLE), a complex autoimmune disorder with high morbidity and mortality. Diagnosis and monitoring of LN patients still rely on renal biopsy, a procedure that exposes patients to a variety of risks and is not capable of providing longitudinally information about disease prognosis. In this review, we summarized current data of recent promising biomarkers developed in the precision medicine era, particularly under genomic, transcriptomic, proteomic, and metabolomic techniques. Genome-wide association studies have been evaluating the role of endogenous elements beyond the autoimmunity in LN. Transcriptomic methods, including single-cell sequencing, are potential tools in identifying inflammatory signatures, miRNAs, and gene expression. Proteomic measures, including anti-C1q antibodies, cytokines, TLRs, VCAM-1, NGAL osteopontin, angiostatin, have been considered helpful to provide a more profound comprehension of the disease pathogenic processes. Metabolomic approaches may identify several abnormal metabolite profiles related to the impairment of cellular functions. Together, these accurate, non-invasive, and moderate-cost propedeutic resources may be the novel tools for recognizing, distinguishing, and predicting LN progression and prognosis. Furthermore, omics evaluation may also predict responsiveness to treatment and, consequently, change the way we manage LN cases in the near future.

Background: The Renin-Angiotensin System (RAS) comprises a complex molecular cascade with two counter-regulatory axes, the classical and the alternative. Angiotensin II and Angiotensin-(1-7), the main peptides of the RAS, exert opposite effects in multiple organs and systems, including the cardiovascular, renal, pulmonary, and immune systems. Strong evidence supports the hypothesis of a local RAS in the Central Nervous System (CNS) and its modulatory roles in neuroendocrinology and neurotransmission. Objective: In this narrative review, we provide a comprehensive approach to experimental and clinical data regarding RAS molecule expression and their possible roles in the physiology and physiopathology of CNS diseases. Methods: This non-systematic review summarizes evidence on RAS implications in CNS diseases and their possible relationships with COVID-19. Results: We divided the possible RAS mechanisms in distinct conditions during the lifespan, approaching from congenital infections to neurodegenerative alterations, passing through mood disorders and cerebrovascular diseases. We also gathered current evidence about the possible effects of RAS in Covid-19, particularly in cases with neurological manifestations. Conclusion: Although there are limitations and controversies, the analysis of RAS mechanisms in the CNS certainly represents an interesting field of research. However, further investigation is necessary to support the noteworthy interactions and provide a better comprehension of the cross-talk between RAS and the CNS. Investigations in this research field may shed light on the novel therapeutic targets.

Background: The identification of vulnerable subgroups and risk factors associated with the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) are of utmost importance in a pandemic scenario. Potential interactions between renin-angiotensin system (RAS), immune markers and COVID-19 play a role in disease outcome in specific groups of patients. Objective: This review aimed to describe the particularities of the RAS and the immune system profile of particular subgroups of patients. Methods: This non-systematic review summarizes evidence on SARS-CoV-2 infection in specific subgroups of patients and possible relationships between immune system, RAS and the pathophysiology of COVID-19. Results: The RAS and the immune system exert a role in the pathogenesis and prognosis of COVID-19, mainly in cases of hypertension, diabetes, obesity and other chronic diseases. The overactivation of the ACE/Ang II/AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID-19. Likewise, pregnant women and elderly patients usually display immune responses that are less effective in withstanding exposition to viruses, while children are relatively protected against severe complications of COVID-19. Women, conversely, exhibit stronger antiviral responses and are less sensitive to the effects of increased Ang II. Future Perspectives: The recognition of vulnerable subgroups and risk factors for disease severity is essential to better understand the pandemic. Precision medicine tools, including proteomics and metabolomics approaches, identified metabolic patterns of the severe form of disease and might be the alternative to diagnose, evaluate and predict the prognosis and the efficiency of therapies.

Background:: The Coronavirus Disease 2019 (COVID-19) is becoming the major health issue in recent human history with thousands of deaths and millions of cases worldwide. Newer research and old experience with other coronaviruses highlighted a probable underlying mechanism of disturbance of the renin-angiotensin system (RAS) that is associated with the intrinsic effects of SARS-CoV-2 infection. Objective:: In this review, we aimed to describe the intimate connections between the RAS components, the immune system and COVID-19 pathophysiology. Methods:: This non-systematic review article summarizes recent evidence on the relationship between COVID-19 and the RAS. Results:: Several studies have indicated that the downregulation of membrane-bound ACE2 may exert a key role for the impairment of immune functions and for COVID-19 patients’ outcomes. The downregulation may occur by distinct mechanisms, particularly: (1) the shedding process induced by the SARS-CoV-2 fusion pathway, which reduces the amount of membrane-bound ACE2, stimulating more shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor with the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on the immune system, which leads to a reduction of ACE2 receptor expression. Conclusion:: Recent research provides evidence of a reduction of the components of the alternative RAS axis, including ACE2 and Angiotensin-(1-7). In contrast, increased levels of Angiotensin II can activate the AT1 receptor in several organs. Consequently, increased inflammation, thrombosis and angiogenesis occur in patients infected with SARS-COV-2. Attention should be paid to the interactions of the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.

A 75-year-old man was hospitalised for bronchoscopy with biopsy due to a suspicious pulmonary mass at chest tomography. He had significant dyspnoea, constipation, nausea, vomiting, anorexia and a 33% loss of weight in the past 3 months. Biopsy revealed a pulmonary squamous cell carcinoma, which was inoperable. Tramadol used at home for 3 months was replaced by morphine on admission. The patient remained constipated despite prokinetics and laxatives, leading to the diagnostic hypothesis of paraneoplastic motility disorder and opioid-induced constipation. Abdominal tomography ruled out the possibility of mechanical obstruction. As complications, the patient presented superior vena cava syndrome and opioid (morphine) intoxication. The patient died a few days later. The management of this case highlights the importance of multidisciplinary care and the challenges of palliative oncology care. Paraneoplastic motility disorder must always be considered among the mechanisms of intestinal dysfunction in patients with advanced oncological disease.

Involvement of the kidneys by lupus nephritis (LN) is one of the most severe clinical manifestations seen in individuals with systemic lupus erythematosus (SLE). LN is more frequent and severe in pediatric patients and has been associated with higher morbidity and mortality rates. This narrative review aimed to describe the general aspects of LN and its particularities when affecting children and adolescents, while focusing on the disease's etiopathogenesis, clinical manifestations, renal tissue alterations, and treatment options.