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Introduction: Fostemsavir is a gp120-directed attachment inhibitor approved for heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. We provide detailed week 240 safety results from the BRIGHTE study and evaluate the impact of immune recovery on safety outcomes. Methods: The phase 3 BRIGHTE trial is ongoing; data for this analysis were collected from the first participant's first visit (February 23, 2015) through the last participant's last visit for week 240 (March 22, 2021). Safety endpoints were assessed in participants who received fostemsavir + optimized background therapy. In participants with baseline CD4+ T-cell count <200 cells/mm3, exposure-adjusted adverse event (AE) rates were assessed among subgroups with or without CD4+ T-cell count ≥200 cells/mm3 at any time during 48-week analysis periods through week 192. Results: Through a median of 258 weeks (range, 0.14-319) of treatment, discontinuations due to AEs occurred in 30/371 (8%) participants. Serious AEs were reported in 177/371 (48%) participants, including 16 drug-related events in 13 (4%) participants. Thirty-five (9%) deaths occurred, primarily related to AIDS or acute infections. COVID-19-related events occurred in 25 (7%) participants; all resolved without sequelae. Among participants with baseline CD4+ T-cell count <200 cells/mm3, 122/162 (75%) achieved CD4+ T-cell count ≥200 cells/mm3 at week 192. Exposure-adjusted AE rates were markedly lower among participants achieving CD4+ T-cell count ≥200 cells/mm3 at any time vs those sustaining <200 cells/mm3. No new AIDS-defining events were reported after week 48 in participants with CD4+ T-cell count ≥200 cells/mm3. Conclusions: Cumulative safety findings through the BRIGHTE 240-week interim analysis are consistent with other trials in HTE participants with advanced HIV-1 and comorbid disease. Reduced rates of AIDS-defining events and AEs were observed in participants with immunologic recovery on fostemsavir-based treatment. Clinical trial number: NCT02362503, https://clinicaltrials.gov/study/NCT02362503.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Adulto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Feminino , Masculino , Contagem de Linfócito CD4 , Pessoa de Meia-Idade , HIV-1/imunologia , HIV-1/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Organofosfatos/uso terapêutico , Organofosfatos/efeitos adversos , COVID-19/imunologia , SARS-CoV-2/imunologia , Resultado do Tratamento , Carga Viral , PiperazinasRESUMO
BACKGROUND: The presence of "muddy" brown granular casts (MBGC) in the urine sediment is pathognomonic for acute tubular injury (ATI). Although MBGC have been noted for years, there are no reports regarding their length nor width. The objective of this study was to measure MBGC using images obtained by light microscopy and investigate associations with clinically relevant parameters. METHODS: Patients with diagnosis of ATI as evidenced by visualization of abundant MBGC (>30% low power fields) were sampled. Bright-field images were measured using ImageJ. Twenty-five patients were included: 44% women; median age 64 yrs; 52% white, 36% black. Mean MBGC width (n = 350) was 34.4 ± 13.1 µm (range: 9 to 110 µm). RESULTS: Mean MBGC length was 98.7 ± 42.7 µm (range: 33 to 317 µm). Based on a previous report of cortical tubular diameters, MBGC width corresponded well with the median reported range. MBGC width was positively correlated with patient height (ρ=0.41, p=0.04), and length was positively correlated with fractional excretion of sodium (ρ=0.57. p=0.02) and urine chloride concentration (ρ=0.90, p=0.001). Mean MBGC length was negatively correlated with age (ρ=-0.47, p=0.02) and urine phosphate concentration (ρ=-0.72, p=0.03). There were no differences between cases that required renal replacement therapy (RRT, n =10) and those that did not require RRT (n=15). CONCLUSION: This is the first study reporting dimensions of MBGC from cases with ATI. Clinical implications of these observations require further study.
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Injúria Renal Aguda , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Injúria Renal Aguda/patologia , Injúria Renal Aguda/urina , Adulto , Idoso de 80 Anos ou maisAssuntos
Doenças Cardiovasculares , Bases de Dados Factuais , Glomerulosclerose Segmentar e Focal , Humanos , Doenças Cardiovasculares/mortalidade , Masculino , Feminino , Adulto , Glomerulosclerose Segmentar e Focal/mortalidade , Estados Unidos/epidemiologia , Insuficiência Renal/mortalidade , Insuficiência Renal/epidemiologia , Pessoa de Meia-Idade , Causas de Morte , Adulto JovemRESUMO
BACKGROUND: Leptospirosis is a zoonosis caused by pathogenic species of bacteria belonging to the genus Leptospira. Most studies infer the epidemiological patterns of a single serogroup or aggregate all serogroups to estimate overall seropositivity, thus not exploring the risks of exposure to distinct serogroups. The present study aims to delineate the demographic, socioeconomic and environmental factors associated with seropositivity of Leptospira serogroup Icterohaemorraghiae and serogroup Cynopteri in an urban high transmission setting for leptospirosis in Brazil. METHODS/PRINCIPAL FINDINGS: We performed a cross-sectional serological study in five informal urban communities in the city of Salvador, Brazil. During the years 2018, 2020 2021, we recruited 2.808 residents and collected blood samples for serological analysis using microagglutination assays. We used a fixed-effect multinomial logistic regression model to identify risk factors associated with seropositivity for each serogroup. Seropositivity to Cynopteri increased with each year of age (OR 1.03; 95% CI 1.01-1.06) and was higher in those living in houses with unplastered walls (exposed brick) (OR 1.68; 95% CI 1.09-2.59) and where cats were present near the household (OR 2.00; 95% CI 1.03-3.88). Seropositivity to Icterohaemorrhagiae also increased with each year of age (OR 1.02; 95% CI 1.01-1.03) and was higher in males (OR 1.51; 95% CI 1.09-2.10), in those with work-related exposures (OR 1.71; 95% CI 1.10-2.66) or who had contact with sewage (OR 1.42; 95% CI 1.00-2.03). Spatial analysis showed differences in distribution of seropositivity to serogroups Icterohaemorrhagiae and Cynopteri within the five districts where study communities were situated. CONCLUSIONS/SIGNIFICANCE: Our data suggest distinct epidemiological patterns associated with the Icterohaemorrhagiae and Cynopteri serogroups in the urban environment at high risk for leptospirosis and with differences in spatial niches. We emphasize the need for studies that accurately identify the different pathogenic serogroups that circulate and infect residents of low-income areas.
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Leptospira interrogans , Leptospira , Leptospirose , Sorogrupo , Leptospirose/epidemiologia , Leptospirose/microbiologia , Leptospirose/transmissão , Brasil/epidemiologia , Humanos , Masculino , Adulto , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Leptospira/classificação , Leptospira/imunologia , Leptospira/isolamento & purificação , Adulto Jovem , Adolescente , Leptospira interrogans/imunologia , Leptospira interrogans/classificação , Leptospira interrogans/isolamento & purificação , Fatores de Risco , Estudos Soroepidemiológicos , População Urbana , Anticorpos Antibacterianos/sangue , Animais , Criança , IdosoRESUMO
Hepatorenal syndrome type 1 (HRS-1) is a unique form of acute kidney injury that affects individuals with decompensated cirrhosis with ascites. The primary mechanism leading to reduction of kidney function in HRS-1 is hemodynamic in nature. Cumulative evidence points to a cascade of events that led to a profound reduction in kidney perfusion. A state of increased intrahepatic vascular resistance characteristic of advanced cirrhosis and portal hypertension is accompanied by maladaptive peripheral arterial vasodilation and reduction in systemic vascular resistance and mean arterial pressure. As a result of a fall in effective arterial blood volume, there is a compensatory activation of the sympathetic nervous system and the renin-angiotensin system, local renal vasoconstriction, loss of renal autoregulation, decrease in renal blood flow, and ultimately a fall in glomerular filtration rate. Systemic release of nitric oxide stimulated by the fibrotic liver, bacterial translocation, and inflammation constitute key components of the pathogenesis. While angiotensin II and noradrenaline remain the critical mediators of renal arterial and arteriolar vasoconstriction, other novel molecules have been recently implicated. Although the above-described mechanistic pathway remains the backbone of the pathogenesis of HRS-1, other noxious elements may be present in advanced cirrhosis and likely contribute to the renal impairment. Direct liver-kidney crosstalk via the hepatorenal sympathetic reflex can further reduce renal blood flow independently of the systemic derangements. Tense ascites may lead to intraabdominal hypertension and abdominal compartment syndrome. Cardio-hemodynamic processes have also been increasingly recognized. Porto-pulmonary hypertension, cirrhotic cardiomyopathy, and abdominal compartment syndrome may lead to renal congestion and complicate the course of HRS-1. In addition, a degree of ischemic or toxic (cholemic) tubular injury may overlap with the underlying circulatory dysfunction and further exacerbate the course of acute kidney injury. Improving our understanding of the pathogenesis of HRS-1 may lead to improvements in therapeutic options for this seriously ill population.
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Síndrome Hepatorrenal , Humanos , Síndrome Hepatorrenal/fisiopatologia , Síndrome Hepatorrenal/terapia , Síndrome Hepatorrenal/etiologia , Cirrose Hepática/fisiopatologia , Cirrose Hepática/complicações , Circulação Renal/fisiologia , Hemodinâmica/fisiologia , Sistema Renina-Angiotensina/fisiologia , Rim/fisiopatologia , Hipertensão Portal/fisiopatologia , Ascite/fisiopatologiaRESUMO
The adoption of precision technologies on dairy farms has increased significantly in recent decades, leading to the challenge of providing employees with resources to maximize the efficient use of these tools. The objective of this study was to explore how dairy farm employees perceive the available precision technologies and to identify possible challenges they face when adapting to their use at the farm. An online survey consisting of four sections (employee demographics, precision technologies in use, perception of these technologies, and opportunities for adapting to technology use) was completed from September to December 2022 by 266 farm employees from three dairies operated under similar management. Most of the respondents were identified as male (72.2%), Hispanic or Latino (92.5%), aged between 21 and 30 (39.1%) or 31 and 40 yr (36.8%), with a bachelor's degree (34.6%) or completion of middle school (29.3%) and having basic or no English proficiency (74%). Overall, the respondents indicated being comfortable (95.6%) with and understanding (91.8%) the technology they use. Employees recognized precision technology as a tool that helps them to be more efficient (93.7%), identifying the technologies' benefits (92.1%). However, challenges for adapting to these technologies included personal limitations, such as not knowing the language of the technology (31%), visual impairments (24%), light sensitivity (14%), and not being able to read (7%). Environmental limitations were also recognized and included cold weather (64.3%), wind (46%), and surroundings that were too dark (31%) or too bright (21%). Significant associations between perception of the technology and age, level of education, and English proficiency were identified. Respondents indicated their desire to learn more about precision technologies implemented at work, which could eventually lead to improved efficiency at the dairy operation through innovations in the way users interact with these technologies, increasing employees' motivation. This study provides insights that could assist the dairy industry in addressing challenges and enhancing opportunities for a more efficient use of precision technologies at dairy farms.
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Tick-borne disease burdens are increasing globally, impacting mostly rural and vulnerable communities. Among the most important emerging tick-borne pathogens are the Rickettsia species within the spotted fever group (SFGR) because of their genetic diversity and high lethality rate. Colombia is highly affected by SFGR despite not being reportable diseases; thus, research and clinical management are neglected. Although some departments have demonstrated high seroprevalence rates, in others, such as Boyacá Department, seroprevalence is unknown. Rickettsioses have not been described in Boyacá since 1943, and conversations with local physicians raised suspicions of recent undiagnosed disease compatible with rickettsiosis in some rural areas of the department, warranting epidemiological investigation. Using biobanked human and canine samples from a previous 2021 vector-borne disease study in Miraflores municipality, Boyacá, we had an opportunity to unearth SFGR's exposure in the region. Samples were evaluated using IgG indirect fluorescent assays against SFGR and complemented by survey questionnaires evaluating associated factors. Findings yielded first-time SFGR serological evidence in Boyacá with a 26.5% seroprevalence among dogs and a 20.4% among humans. Human and dog seroprevalences were positively associated, suggesting the presence of domestic transmission. Owning a greater number of domestic animals (prevalence ratio adjusted for all measured factors [aPR], 1.52) and living near crop fields (aPR, 7.77) were associated with an increased likelihood of household seropositivity. Our findings are consistent with the literature in Colombia, uncovering a suspected region where the disease is endemic. Future studies are warranted to continue defining high-risk areas to determine public health intervention plans.
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Anticorpos Antibacterianos , Doenças do Cão , Rickettsia , Rickettsiose do Grupo da Febre Maculosa , Cães , Animais , Estudos Soroepidemiológicos , Humanos , Colômbia/epidemiologia , Estudos Transversais , Doenças do Cão/epidemiologia , Doenças do Cão/microbiologia , Masculino , Feminino , Adulto , Anticorpos Antibacterianos/sangue , Rickettsiose do Grupo da Febre Maculosa/epidemiologia , Rickettsiose do Grupo da Febre Maculosa/microbiologia , Pessoa de Meia-Idade , Rickettsia/imunologia , Adolescente , Adulto Jovem , Idoso , Criança , Imunoglobulina G/sangueRESUMO
Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.
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Injúria Renal Aguda , Síndrome Hepatorrenal , Cirrose Hepática , Humanos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Cirrose Hepática/complicações , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/terapia , Síndrome Hepatorrenal/diagnóstico , Ascite/etiologia , Ascite/terapia , Ascite/diagnóstico , ConsensoRESUMO
A 72-year-old man with peripheral arterial disease, an atrophic left kidney, and prior right renal chimney stent as part of a complex endovascular abdominal aortic aneurysm repair presented to our emergency department with right flank pain and anuria resulting from right artery occlusion. His serum creatinine on admission was 7.5 mg/dL. Computed tomography angiography 6 days after the onset of his symptoms revealed complete occlusion of the right renal artery stent. Percutaneous thrombectomy was performed restored renal blood flow. The urine flow started the following day, and his serum creatinine decreased to 3.5 mg/dL 7 days after discharge.
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This work analyzes hemodynamic phenomena within the aorta of two elderly patients and their impact on blood flow behavior, particularly affected by an endovascular prosthesis in one of them (Patient II). Computational Fluid Dynamics (CFD) was utilized for this study, involving measurements of velocity, pressure, and wall shear stress (WSS) at various time points during the third cardiac cycle, at specific positions within two cross sections of the thoracic aorta. The first cross-section (Cross-Section 1, CS1) is located before the initial fluid bifurcation, just before the right subclavian artery. The second cross-section (Cross-Section 2, CS2) is situated immediately after the left subclavian artery. The results reveal that, under regular aortic geometries, velocity and pressure magnitudes follow the principles of fluid dynamics, displaying variations. However, in Patient II, an endoprosthesis near the CS2 and the proximal border of the endoprosthesis significantly disrupts fluid behavior owing to the pulsatile flow. The cross-sectional areas of Patient I are smaller than those of Patient II, leading to higher flow magnitudes. Although in CS1 of Patient I, there is considerable variability in velocity magnitudes, they exhibit a more uniform and predictable transition. In contrast, CS2 of Patient II, where magnitude variation is also high, displays irregular fluid behavior due to the endoprosthesis presence. This cross-section coincides with the border of the fluid bifurcation. Additionally, the irregular geometry caused by endovascular aneurysm repair contributes to flow disruption as the endoprosthesis adjusts to the endothelium, reshaping itself to conform with the vessel wall. In this context, significant alterations in velocity values, pressure differentials fluctuating by up to 10%, and low wall shear stress indicate the pronounced influence of the endovascular prosthesis on blood flow behavior. These flow disturbances, when compounded by the heart rate, can potentially lead to changes in vascular anatomy and displacement, resulting in a disruption of the prosthesis-endothelium continuity and thereby causing clinical complications in the patient.
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Chemosensor technology for trace gases in the air always aims to identify these compounds and then measure their concentrations. For identification, traceable methods are sparse and relate to large appliances such as mass spectrometers. We present a new method that uses the alternative traceable measurement of the ionization energies of trace gases in a way that can be miniaturized and energetically tuned. We investigate the achievable performance. Since tunable UV sources are not available for photoionization, we take a detour via impact ionization with electrons, which we generate using the photoelectric effect and bring to sharp, defined energies on a nanoscale in the air. Electron impact ionization is thus possible at air pressures of up to 900 hPa. The sensitivity of the process reaches 1 ppm and is equivalent to that of classic PID. With sharpened energy settings, substance identification is currently possible with an accuracy of 30 meV. We can largely explain the experimental observations with the known quantum mechanical models.
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Rickettsioses and leptospirosis are infectious diseases that are often underdiagnosed due to a lack of knowledge about their epidemiology, pathophysiology, diagnosis, management, among others. Objetive: to characterize the seroprevalence and seroincidence of both Rickettsia and Leptospira agents and determine the risk factors for these outcomes in rural areas of Urabá, Antioquia. Methods: a secondary data analysis using information on Rickettsia and Leptospira exposure from a prior prospective study that explored sociocultural and ecological aspects of Rickettsia infection in rural Urabá, Colombia. A multinomial mixed logistic regression model was employed to analyze factors linked to seroprevalent cases of Rickettsia, Leptospira and both, along with descriptive analyses of seroincident cases. Results: the concomitant seroprevalence against Rickettsiaand Leptospira was 9.38% [95%CI 6.08%-13.37%] (56/597). The factors associated with this seroprevalence were age (ORa= 1.02 [95%CI 1.007-1.03]), male gender (ORa= 3.06 [95%CI 1.75-5.37]), fever history (ORa= 1.71 [95%CI 1.06-2.77]) the presence of breeding pigs (ORa= 2.29 [95%CI 1.36-3.88]), peridomicile yucca crops(ORa= 2.5 [95%CI 1.1-5.62]), and deforestation practices(ORa= 1.74 [95%CI 1.06-2.87]). The concomitant seroincidence against Rickettsia and Leptospira was 1.09% (3/274) [95%CI 0.29%-4.05%], three cases were female, with a median age of 31.83 years-old (IQR 8.69-56.99). At the household level, all the seroincident cases had households built partially or totally with soil floors, wooden walls, and zinc roofs. Two seroincident cases described the presence of equines, canines, and domestic chickens in intra or peri-domicile. Finally, two cases were exposed to synanthropic rodents, and one case to tick infestation. Conclusion: there is evidence of seroprevalent and seroincident cases of seropositivity against both Rickettsia and Leptospira in rural areas of Urabá, Colombia. These findings can help improve public health surveillance systems in preventing, detecting, and attending to the different clinical cases caused by these pathogens.
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Individuals with liver disease are susceptible to pathophysiological derangements that lead to kidney dysfunction. Patients with advanced cirrhosis and acute liver failure (ALF) are at risk of developing acute kidney injury (AKI). Hepatorenal syndrome type 1 (HRS-1, also called HRS-AKI) constitutes a form of AKI unique to the state of cirrhosis and portal hypertension. Although HRS-1 is a condition primarily characterized by marked renal vasoconstriction and kidney hypoperfusion, other pathogenic processes, such as acute tubular injury and renal vein congestion, can overlap and further complicate the course of HRS-1. ALF can lead to AKI through mechanisms that involve systemic inflammation, direct drug toxicity, or bile acid-induced tubulopathy. In addition, the growing prevalence of nonalcoholic steatohepatitis is changing the spectrum of chronic kidney disease in cirrhosis. In this installment of AJKD's Core Curriculum in Nephrology, we explore the underpinnings of how cirrhosis, ALF, acute cholestasis, and post-liver transplantation can be associated with various forms of acute, subacute, or chronic kidney diseases. We navigate through the recommended therapies for each condition, including supportive care, pharmacological interventions, kidney replacement therapy, and organ transplantation. Finally, key acid-base and electrolyte disorders associated with hepatobiliary disease are also summarized.
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Injúria Renal Aguda , Síndrome Hepatorrenal , Falência Hepática , Humanos , Rim/patologia , Cirrose Hepática/complicações , Síndrome Hepatorrenal/etiologia , Síndrome Hepatorrenal/terapia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Falência Hepática/complicações , Falência Hepática/patologiaRESUMO
BACKGROUND: Inflammation may promote atrial fibrillation (AF) recurrence after catheter ablation. This study aimed to evaluate a short-term anti-inflammatory treatment with colchicine following ablation of AF. METHODS: Patients scheduled for ablation were randomized to receive colchicine 0.6 mg twice daily or placebo for 10 days. The first dose of the study drug was administered within 4 hours before ablation. Atrial arrhythmia recurrence was defined as AF, atrial flutter, or atrial tachycardia >30 s on two 14-day Holters performed immediately and at 3 months following ablation. RESULTS: The modified intention-to-treat population included 199 patients (median age, 61 years; 22% female; 70% first procedure) who underwent radiofrequency (79%) or cryoballoon ablation (21%) of AF. Antiarrhythmic drugs were prescribed at discharge in 149 (75%) patients. Colchicine did not prevent atrial arrhythmia recurrence at 2 weeks (31% versus 32%; hazard ratio [HR], 0.98 [95% CI, 0.59-1.61]; P=0.92) or at 3 months following ablation (14% versus 15%; HR, 0.95 [95% CI, 0.45-2.02]; P=0.89). Postablation chest pain consistent with pericarditis was reduced with colchicine (4% versus 15%; HR, 0.26 [95% CI, 0.09-0.77]; P=0.02) and colchicine increased diarrhea (26% versus 7%; HR, 4.74 [95% CI, 1.95-11.53]; P<0.001). During a median follow-up of 1.3 years, colchicine did not reduce a composite of emergency department visit, cardiovascular hospitalization, cardioversion, or repeat ablation (29 versus 25 per 100 patient-years; HR, 1.18 [95% CI, 0.69-1.99]; P=0.55). CONCLUSIONS: Colchicine administered for 10 days following catheter ablation did not reduce atrial arrhythmia recurrence or AF-associated clinical events, but did reduce postablation chest pain and increase diarrhea.
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Fibrilação Atrial , Ablação por Cateter , Colchicina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/prevenção & controle , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Dor no Peito/prevenção & controle , Colchicina/efeitos adversos , Colchicina/uso terapêutico , Diarreia/etiologia , Recidiva , Resultado do TratamentoRESUMO
Lysosomal storage disorders (LSDs) are a group of monogenic condition, with many characterized by an enzyme deficiency leading to the accumulation of an undegraded substrate within the lysosomes. For those LSDs, postnatal enzyme replacement therapy (ERT) represents the standard of care, but this treatment has limitations when administered only postnatally because, at that point, prenatal disease sequelae may be irreversible. Furthermore, most forms of ERT, specifically those administered systemically, are currently unable to access certain tissues, such as the central nervous system (CNS), and furthermore, may initiate an immune response. In utero enzyme replacement therapy (IUERT) is a novel approach to address these challenges evaluated in a first-in-human clinical trial for IUERT in LSDs (NCT04532047). IUERT has numerous advantages: in-utero intervention may prevent early pathology; the CNS can be accessed before the blood-brain barrier forms; and the unique fetal immune system enables exposure to new proteins with the potential to prevent an immune response and may induce sustained tolerance. However, there are challenges and limitations for any fetal procedure that involves two patients. This article reviews the current state of IUERT for LSDs, including its advantages, limitations, and potential future directions for definitive therapies.