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Journal of Cystic Fibrosis : Official... Jun 2024To study the prevalence of cystic fibrosis related liver disease (CFLD) as defined by ultrasound (US) and describe difference in clinical and radiological features in...
AIMS
To study the prevalence of cystic fibrosis related liver disease (CFLD) as defined by ultrasound (US) and describe difference in clinical and radiological features in those with CFLD and those without CFLD (nCFLD); with and without portal hypertension (PHT and nPHT).
METHODS
Children with CF (CwCF) from our clinic who had regular screening liver US from 3 years of age were included. Liver parenchyma findings were classified into normal, homogeneous, heterogeneous and nodular. For our study, we defined PHT as US evidence of splenomegaly and/or ascites, abnormal portal flow, varices, ligamentum teres recanalization if present. Demographic, clinical, nutritional and lung function between the two groups-CFLD/nCFLD; and subgroups- PHT and nPHT were compared. Gamma glutamyl transferase (GGT)/ platelet ratio (GPR) as a marker of fibrosis was measured.
RESULTS
From 227 CwCF,40 (17 %) were excluded (below the age of 3 years or alternative cause of liver disease). Of the remaining 187, 107 (57 %) had a normal US, 80 (43 %) had CFLD; 25 (13.4 %) had PHT. There was no significant difference in demographics, BMI-z score, lung function, presence of gastrostomy or pancreatic insufficiency in CFLD vs nCFLD and PHT vs nPHT. CF related diabetes mellitus (CFRD) was significantly associated with CFLD vs nCFLD (P = 0.0086). GGT was higher and platelet count was lower in PHT vs nPHT (P = 0.0256 and P = 0.0001). Nodularity was strongly associated with an elevated GPR (P = 0.016). There was a strong association between nodularity on US and PHT (P = 0.0006).
CONCLUSION
Nodularity is a clear marker for advanced liver disease with higher scores for a non-invasive marker for fibrosis. There was no difference in nutrition and FEV1 between advanced liver disease and absent/ milder liver disease.
PubMed: 38942721
DOI: 10.1016/j.jcf.2024.06.008 -
Emergency Radiology Jun 2024Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic... (Review)
Review
Ectopic varices account for 5% of variceal bleedings and occur outside the gastro-esophageal region. This review evaluates the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) for ectopic variceal management. A comprehensive search through PubMed, Scopus, Web of Science, and Embase was conducted until January 16, 2023, using relevant keywords. Case reports and case series with fewer than 10 patients on TIPS for ectopic variceal management were included. The quality assessment followed the Joanna Briggs Institute checklist for case reports. This systematic review evaluated 43 studies involving 50 patients with ectopic varices undergoing TIPS. Patients had a mean age of 54.3 years, half were female, and two were pregnant. Alcoholic liver disease (48%) and hepatitis C infection (26%) were common causes of portal hypertension. Ascites and splenomegaly were reported in 32% and 28% of the patients, respectively. Rectal, oral, and stomal variceal bleeding accounted for 62%, 16%, and 22% of the patients, respectively. Ectopic varices were mainly located in the duodenum (28%) and rectum (26%) regions. Complications affected 42% of the patients, re-bleeding in eleven and hepatic encephalopathy in seven. The follow-up lasted 12 months on average, and finally, 5 received a liver transplant. Mortality post-TIPS was 18%. Despite complications and a notable mortality rate, favorable outcomes were observed in almost half of the patients with ectopic variceal bleeding managed with TIPS. Further research is warranted to refine strategies and improve patient outcomes.
PubMed: 38935315
DOI: 10.1007/s10140-024-02258-6 -
Pharmaceutics Jun 2024Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell...
Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell infiltration. Photodynamic therapy (PDT) remains underutilized in the treatment of psoriasis despite its potential as a promising and effective therapeutic approach. This study aimed to explore the efficacy of zinc phthalocyanine (ZnPc) and its sugar conjugates as potential antipsoriatic agents. We successfully synthesized protected and unprotected sugar-conjugated zinc phthalocyanines and evaluated their potential against cytokine-stimulated HaCaT keratinocytes, as well as an established IMQ psoriasis-like in vivo model. Tetrasubstituted protected glucose-ZnPc (Glu-4-ZnPc-P) demonstrated superior phototoxicity (IC50 = 2.55 µM) compared to unprotected glucose conjugate (IC50 = 22.7 µM), protected galactose-ZnPc (IC50 = 7.13 µM), and free ZnPc in cytokine-stimulated HaCaT cells (IC50 = 5.84 µM). Cellular uptake analysis revealed that IL-17A, a cytokine that plays a central role in the pathogenesis of psoriasis, enhanced unprotected Glu-4-ZnPc uptake by 56.3%, while GLUT1 inhibitor BAY-876 reduced its accumulation by 23.8%. Intracellular ROS generation following Glu-4-ZnPc-P-PDT was significantly increased after stimulation with IL-17A, correlating with in vitro photocytotoxicity. In vivo PDT using Glu-4-ZnPc-P exhibited significant improvement in Psoriasis Area and Severity Index (PASI), inhibiting splenomegaly and restoring normal skin morphology. This study highlights sugar-conjugated zinc phthalocyanines as potential candidates for targeted PDT in psoriasis, providing a basis for further clinical investigations.
PubMed: 38931958
DOI: 10.3390/pharmaceutics16060838 -
Medicina (Kaunas, Lithuania) Jun 2024: Prolidase deficiency (PD) is a rare, life-threatening, genetically determined disease with an incidence of 1-2 cases per 1 million births. The disease inhibits... (Observational Study)
Observational Study
: Prolidase deficiency (PD) is a rare, life-threatening, genetically determined disease with an incidence of 1-2 cases per 1 million births. The disease inhibits collagen synthesis, which leads to organ and systems failure, including hepato- and splenomegaly, immune disorders, chronic ulcerative wounds, respiratory infections, and pulmonary fibrosis. The complexity of the problems associated with this disease necessitates a comprehensive approach and the involvement of an interdisciplinary team. The objective was to present the treatment and care plan, as well as complications of PD, in a young woman following admission to an intensive care unit (ICU). : A retrospective observational single-case study. : A 26-year-old woman with PD was hospitalized in the ICU for acute respiratory failure. The presence of difficult-to-heal extensive leg ulcers and the patient's immunocompromised condition resulted in the development of sepsis with multiple organ failure (respiratory and circulatory, liver and kidney failure). Complex specialized treatment consisting of wound preparation, limb amputation, the minimization of neuropathic pain, mechanical ventilation, renal replacement therapy, circulatory stabilization, and the prevention of complications of the disease and of therapy were applied. On the 83rd day of hospitalization, the patient expired. : Despite the use of complex treatment and care, due to the advanced nature of the disease and the lack of therapies with proven efficacy, treatment was unsuccessful. There is a need for evidence-based research to develop effective treatment guidelines for PD.
Topics: Humans; Female; Adult; Multiple Organ Failure; Intensive Care Units; Sepsis; Prolidase Deficiency; Retrospective Studies; Fatal Outcome
PubMed: 38929623
DOI: 10.3390/medicina60061006 -
Diagnostics (Basel, Switzerland) Jun 2024The liver, given its role as the central metabolic organ, is involved in many inherited metabolic disorders, including lysosomal storage diseases (LSDs). The aim of this... (Review)
Review
The liver, given its role as the central metabolic organ, is involved in many inherited metabolic disorders, including lysosomal storage diseases (LSDs). The aim of this manuscript was to provide a comprehensive overview on liver involvement in LSDs, focusing on clinical manifestation and its pathomechanisms. Gaucher disease, acid sphingomyelinase deficiency, and lysosomal acid lipase deficiency were thoroughly reviewed, with hepatic manifestation being a dominant clinical phenotype. The natural history of liver disease in the above-mentioned lysosomal disorders was delineated. The importance of Niemann-Pick type C disease as a cause of cholestatic jaundice, preceding neurological manifestation, was also highlighted. Diagnostic methods and current therapeutic management of LSDs were also discussed in the context of liver involvement.
PubMed: 38928715
DOI: 10.3390/diagnostics14121299 -
Surgical Case Reports Jun 2024The safety of laparoscopic hepatectomy for inherited coagulation disorders is unclear; however, the safety of open hepatectomy has been reported in several studies....
BACKGROUND
The safety of laparoscopic hepatectomy for inherited coagulation disorders is unclear; however, the safety of open hepatectomy has been reported in several studies. Herein, we report the first case of a laparoscopic hepatectomy for a patient with von Willebrand Disease (VWD).
CASE PRESENTATION
A 76-year-old male with a history of chronic hepatitis C and VWD type 2B was advised surgical resection of a 4 cm hepatocellular carcinoma in segment 7 of the liver. The patient was diagnosed with VWD in his 40 s due to gastrointestinal bleeding caused by gastric erosion. The von Willebrand factor (VWF) ristocetin cofactor activity was 30%, and VWF large multimer deficiency and increased ristocetin-induced platelet agglutination were observed. The preoperative platelet count was reduced to 3.5 × 10/μL; however, preoperative imaging findings had no evidence of liver cirrhosis, such as any collateral formations and splenomegaly. The indocyanine green retention rate at 15 min was 10%, and his Child-Pugh score was 5 (classification A). Perioperatively, VWF/factor VIII was administered in accordance with our institutional protocol. A laparoscopic partial hepatectomy of the right posterior segment was performed. The most bleeding during surgery occurred during the mobilization of the right lobe of the liver due to inflammatory adhesion between the retroperitoneum and the tumor. Bleeding during parenchymal transection was controlable. The duration of hepatic inflow occlusion was 65 min. The surgical duration was 349 min, and the estimated blood loss was 2150 ml. Four units of red blood cells and fresh frozen plasma were transfused at the initiation of parenchymal transection, and 10 units of platelets were transfused at the end of the parenchymal transection. On postoperative day 1, the transection surface drainage fluid became hemorrhagic, and emergency contrast-enhanced computed tomography showed extravasation in the greater omentum. Percutaneous transcatheter arterial embolization of the omental branch of the right gastroepiploic artery was performed. No further postoperative interventions were required. The patient was discharged on postoperative day 14.
CONCLUSION
The indications for laparoscopic hepatectomy in patients with VWD should be carefully considered, and an open approach may still be the standard approach for patients with VWD.
PubMed: 38926208
DOI: 10.1186/s40792-024-01960-4 -
Expert Opinion on Pharmacotherapy Jun 2024Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, a potential for leukemic... (Review)
Review
INTRODUCTION
Myelofibrosis (MF) is a BCR-ABL-negative myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, cytopenias, a potential for leukemic transformation, and increased mortality. Patients who are ineligible for stem cell transplant rely on pharmacologic therapies of noncurative intent, whose cornerstone consists of JAK inhibitors (JAKi). While current JAKi are efficacious in controlling symptoms and splenic volume, none meaningfully reduce clonal burden nor halt disease progression, and patients oftentimes develop JAKi intolerant, relapsed, or refractory MF. As such, there remains an urgent necessity for second-line options and novel therapies with disease-modifying properties.
AREAS COVERED
In this review, we delineate the mechanistic rationale, along with the latest safety and efficacy data, of investigational JAKi-based MF treatment strategies, with a focus on JAKi monotherapies and combinations of novel agents with approved JAKi. Our literature search consisted of extensive review of PubMed and clinicaltrials.gov.
EXPERT OPINION
A myriad of promising MF-directed therapies are in late-phase studies. Following their approval, treatment selection should be tailored to patient-specific treatment goals and disease characteristics, with an emphasis on combination therapies of JAKi with novel agents of differing mechanistic targets that possess anti-clonal properties, in attempt to alter disease course and concurrently limit dose-dependent JAKi toxicities.
PubMed: 38919983
DOI: 10.1080/14656566.2024.2372453 -
Leukemia Research Jun 2024
PubMed: 38917658
DOI: 10.1016/j.leukres.2024.107543 -
Cureus May 2024Splenic sequestration crisis is a life-threatening complication of sickle cell disease (SCD), characterized by a sudden and huge accumulation of blood in the spleen,...
Splenic sequestration crisis is a life-threatening complication of sickle cell disease (SCD), characterized by a sudden and huge accumulation of blood in the spleen, leading to rapid enlargement and may lead to organ failure. This case report discusses an unusual case of a splenic sequestration crisis in an adult with SCD. The patient's age, Parvovirus B19 infection, and concurrent retrocardiac pneumonia are all things that differentiate this case from our usual presentation. We will be discussing the clinical presentation, diagnostic methods, and management.
PubMed: 38915956
DOI: 10.7759/cureus.60937 -
Cureus May 2024The hemophagocytic syndrome (HS) or hemophagocytic lymphohistiocytosis (HLH) is a syndrome with apoptosis deficiency that results in the impairment of a regulatory...
The hemophagocytic syndrome (HS) or hemophagocytic lymphohistiocytosis (HLH) is a syndrome with apoptosis deficiency that results in the impairment of a regulatory pathway with consequent immune and inflammatory responses. Fever, cytopenias, splenomegaly, and hemophagocytosis are cardinal signs. It may be familial or secondary to infection, autoimmunity, or neoplasia. Impaired natural killer (NK)-cell cytotoxicity is the hallmark of HLH. All genetic defects in familial HLH are related to granule-dependent cytotoxicity. The authors present a 50-year-old black female patient with a history of drepanocytosis who attended the emergency department due to fever, asthenia, lethargy, and hypogastric pain. Her laboratory workup on admission revealed severe pancytopenia. She was ultimately diagnosed with HLH due to sepsis of urinary origin, with a fatal outcome. HLH is a rare and life-threatening syndrome. The delay in its diagnosis due to the variability of the clinical and laboratory findings constitutes the main obstacle to a successful prognosis, as illustrated in this case report.
PubMed: 38910771
DOI: 10.7759/cureus.61015