Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

• MeSH
• Anti-Inflammatory Agents pharmacology   chemistry   MeSH
• Dexamethasone * pharmacology   chemistry   analogs & derivatives   MeSH
• Liver * drug effects   metabolism   MeSH
• Polylactic Acid-Polyglycolic Acid Copolymer * chemistry   MeSH
• Macrophages * drug effects   metabolism   MeSH
• Mice MeSH
• Nanospheres * chemistry   MeSH
• Drug Carriers chemistry   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Východiska: Castlemanova choroba (Castleman disease – CD) nese název po autorovi prvního popisu. Používá se pro ložisko či ložiska charakteru nemaligní lymfoproliferace. Dle rozsahu postižení organizmu se dělí na dvě základní formy, unicentrickou formu (unicentric Castleman disease – UCD) a multicentrickou formu, přičemž UCD je tvořena hyalinně vaskulárním typem CD. Pozorování: Prvním symptomem v popsaném případě UCD byly bolesti vyzařující do levé horní končetiny, obzvláště při pohybu. Vyšetření krční páteře pomocí MR odhalilo jako příčinu patologickou expanzi na pomezí krku a horního mediastina, více vlevo. Cílená biopsie prokázala CD, hyalinně vaskulární typ. Dle PET/CT zobrazení s využitím fluorodeoxyglukózy (FDG-PET/CT) se jednalo o jediné patologické ložisko v těle. Velikost tumorózní rezistence neumožnovala bezpečnou resekci, a tak jediným řešením bylo podávání adjuvantní léčby. Pacientka zahájila léčbu ve složení rituximab 850 mg v den 1 28denního cyklu, cyklofosfamid 600 mg v dny 1 a 15 a dexametazon 20 mg také v dny 1 a 15 28denního cyklu. Pro individuální intoleranci cyklofosfamidu v prvním cyklu bylo podávání tohoto léku přerušeno a od třetího cyklu dostávala místo cyklofosfamidu bendamustin v celkové dávce 100 mg v dny 1 a 15. Výsledky: Zobrazení pomocí FDG-PET/CT po devíti cyklech léčby prokázalo výrazné zmenšení velikosti infiltrátu a zmenšení míry akumulace FDG. To umožnilo týmu hrudního chirurga a kardiochirurga kompletní odstranění až do zdravé tkáně. Závěr: Léčbou volby pro UCD je operační odstranění. V případě, že uložení či velikost ložiska neumožnuje radikální operaci, je možné dosáhnout zmenšení uvedenou medikamentózní léčbou. V popsaném případě kombinace rituximabu, bendamustinu a dexametazonu zmenšila velikost ložiska, což umožnilo jeho kompletní resekci.

Background: Castleman disease (CD) is a historical name derived from the name of the surgeon who first described it. It is used for lesions or foci of the character of non-malignant lymphoproliferative activity. According to the extent of the affliction, it is divided into two basic forms, the unicentric form (UCD) and the multicentric form of Castleman disease, where UCD is formed by the hyaline vascular type of CD. Observation: The first symptom in the described case of UCD was pain radiating to the left upper limb, especially when moving. MRI of the cervical spine revealed pathological expansion on the border between the neck and the upper mediastinum, more on the left. Targeted biopsy showed Castleman disease, hyaline vascular type. According to PET/CT imaging with fluorodeoxyglucose (FDG-PET/CT), it was the only pathological lesion in the body. The size of the tumour resistance did not allow safe resection, so the only solution was to administer adjuvant treatment. The patient started treatment with rituximab 850 mg on day 1 of a 28-day cycle, cyclophosphamide 600 mg on days 1 and 15 and dexamethasone 20 mg, also on days 1 and 15 of a 28-day cycle. Due to individual intolerance of cyclophosphamide in the first cycle, the administration of this drug was discontinued, and from the third cycle onwards, instead of cyclophosphamide, she received bendamustine at a total dose of 100 mg on days 1 and 15. Results: FDG-PET/CT imaging after 9 cycles of treatment showed a marked reduction in the infiltrate size and a decrease in the rate of FDG accumulation. This allowed the team of thoracic and cardiac surgeons to completely remove it down to healthy tissue. Conclusion: The treatment of choice for UCD is surgical removal. If the location or size of the lesion does not allow radical surgery, it is possible to achieve reduction by the mentioned drug treatment. In the case described, the combination of rituximab, bendamustine and dexamethasone reduced the size of the lesion, which allowed its complete resection.

• MeSH
• Bendamustine Hydrochloride pharmacology   therapeutic use   MeSH
• Dexamethasone pharmacology   therapeutic use   MeSH
• Diagnosis, Differential MeSH
• Castleman Disease * diagnosis   drug therapy   classification   MeSH
• Drug Therapy, Combination * methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lymphoproliferative Disorders diagnosis   drug therapy   classification   MeSH
• Rituximab pharmacology   therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Research Support, Non-U.S. Gov't MeSH

Daratumumab, lenalidomid (Revlimid) a dexamethason (DRd) je léčebná kombinace indikovaná pro pacienty s nově diagnostikovaným, ale i relabujícím mnohočetným myelomem. Účinnost DRd v léčbě myelomu nelze zpochybnit. U pacientky, kterou popisuje náš příspěvek, byl diagnostikován kromě myelomu i nekrobiotický xantogranulom (NXG) se závažnými komplikacemi. Vzhledem k raritnímu výskytu této histocytární nemoci není stanoven žádný optimální léčebný postup. S cílem léčby mnohočetného myelomu a s ním spojeného NXG jsme použili režim DRd v kombinaci s intravenózní aplikací imunoglobulinů. Kombinovaná léčba vedla k významné regresi NXG a k vymizení potíží, které byly s NXG spojeny.

Daratumumab, lenalidomid and dexamethason (DRd) is a combination treatment indicated for newly diagnosed as well as relapsed multiple myeloma. The efficacy of DRd in the treatment of myeloma is unquestionable. In the case of the patient described in our report, in addition to myeloma, necrobiotic xanthogranuloma (NXG) with significant complications was also diagnosed. Given the rare occurrence of this histiocytic disease, no optimal treatment protocol has been established. With the aim of myeloma treating and associated NXG, we used the DRd regimen in combination with intravenous administration of immunoglobulins. The combined treatment led to significant regression of NXG and the disappearance of symptoms associated with NXG.

• Keywords
• daratumumab,
• MeSH
• Dexamethasone pharmacology   therapeutic use   MeSH
• Adult MeSH
• Immunoglobulins, Intravenous administration & dosage   pharmacology   therapeutic use   MeSH
• Lenalidomide pharmacology   therapeutic use   MeSH
• Humans MeSH
• Multiple Myeloma * drug therapy   MeSH
• Antibodies, Monoclonal pharmacology   therapeutic use   MeSH
• Necrobiotic Xanthogranuloma * drug therapy   physiopathology   MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Postižení ledvin v rámci Light Chain Depositon Disease (LCDD) je velmi vzácně diagnostikovanou jednotkou. Popisuje- me případ, kdy tato diagnóza byla morfologicky stanovena až v biopsii transplantované ledviny a retrospektivně byla dohledána i v předchozí biopsii ledvin, kde však změny nebyly správně klasifikovány. Biopsie transplantované ledviny byla provedena pro postupně se horšící funkce štěpu. Následné vyšetření, cílené na monoklonální gamapatii, prokázalo zvýšenou sérovou koncentraci volných lehkých řetězců kappa (free light chain – FLC) s maximální hodnotou FLC kappa 226 mg/l a FLC lambda jen 6 mg/l. Poměr FLC kappa / FLC lambda byl jasně patologický, 37 (normalní rozmezí 0,26–1,65). Imunofixační elektroforéza séra a moče byla opakovaně negativní. Cytologické vyšetření kostní dřeně popsalo 8 % patolo- gických plazmatických buněk. Flow-cytometrické vyšetření kostní dřeně prokázalo 0,7 % plazmocytů ze všech jaderných buněk kostní dřeně. Tyto plazmocyty byly ve 100 % klonální, abnormálního fenotypu kappa+. Diagnóza byla uzavřena jako nemaligní gamapatie typu „monoklonální gamapatie renálního významu“ s poškozením ledvin v morfologické formě odpovídající LCDD. Pro léčbu byla zvolena kombinace daratumumabu, bortezomibu, cyklofosfamidu a dexametazonu. Současně pacientka dostávala imunosupresivní léčbu nutnou k zachování funkce transplantované ledviny. Sérová hladina volných lehkých řetězců kappa v průběhu prvních dvou měsíců léčby poklesla pod dolní hranici normy. LCDD je jednou z mnoha forem poškození ledvin, k němuž může dojít při nemaligních gamapatiích. Proto by vyšetření FLC mělo být provedeno vždy v rámci diferenciální diagnostiky každého renálního selhání. Pro poškození ledvin mono- klonálním imunoglobulinem byla akceptována klasifikace vytvořená mezinárodní skupinou The International Kidney and Monoclonal Gammopathy Research Group. Morfology, hodnoticí biopsie ledvin, je vhodné informovat o případné přítomnosti patologické koncentrace FLC anebo M-Ig, aby

Light Chain Deposition Disease (LCDD) is a very rarely diagnosed condition affecting the kidneys. We describe a case where this diagnosis was morphologically confirmed in a biopsy of a transplanted kidney, and retrospectively identified in a previous kidney biopsy where the changes were not correctly classified. The biopsy of the transplanted kidney was performed due to worsening graft function. Subsequent testing focused on monoclonal gammopathy, revealing elevated serum concentrations of free kappa light chains (FLC) with a maximum FLC kappa value of 226 mg/l and FLC lambda at only 6 mg/l. The FLC kappa / FLC lambda ratio was clearly pathological at 37 (normal range 0.26-1.65). Serum and urine immunofixation electrophoresis were repeatedly negative. Bone marrow cytology described 8% pathological plasma cells, and flow cytometry demonstrated 0.7% plasma cells among all nuclear bone marrow cells. These plasma cells were 100% clonal, of the abnormal kappa + phenotype. The diagnosis was thus concluded as a non-malignant gammopathy of the type "monoclonal gammopathy of clinical significance" with renal damage in a morphological form corresponding to LCDD. A combination of daratumumab, bortezomib, cyclophosphamide and dexamethasone was chosen for treatment LCDD. Free light kappa chains decreased below the lower limit of the norm during the first two months of anti-CD38 therapy. LCDD is one of the many forms of kidney damage that can occur in non-malignant gammopathies. Therefore, FLC testing should always be performed as part of the differential diagnosis of renal failure. For kidney damage by monoclonal immunoglobulin, a classification created by The International Kidney and Monoclonal Gammopathy Research Group was accepted. It is advisable to inform the evaluating morphologists of the possible presence of pathological concentrations of FLC and/or M-Ig so that they can focus the diagnosis in this direction, otherwise these rare forms of kidney injury may remain unrecognized.

• Keywords
• daratumumab,
• MeSH
• Bortezomib administration & dosage   therapeutic use   MeSH
• Cyclophosphamide administration & dosage   therapeutic use   MeSH
• Dexamethasone administration & dosage   therapeutic use   MeSH
• Immunoglobulin Light Chains blood   MeSH
• Humans MeSH
• Antibodies, Monoclonal administration & dosage   therapeutic use   MeSH
• Paraproteinemias diagnosis   pathology   therapy   MeSH
• Immunoglobulin Light-chain Amyloidosis * diagnosis   drug therapy   MeSH
• Renal Insufficiency etiology   MeSH
• Aged MeSH
• Kidney Transplantation MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Frontline daratumumab-based triplet and quadruplet standard-of-care regimens have demonstrated improved survival outcomes in newly diagnosed multiple myeloma (NDMM). For patients with transplant-ineligible NDMM, triplet therapy with either daratumumab plus lenalidomide and dexamethasone (D-Rd) or bortezomib, lenalidomide and dexamethasone (VRd) is the current standard of care. This phase 3 trial evaluated subcutaneous daratumumab plus VRd (D-VRd) in patients with transplant-ineligible NDMM or for whom transplant was not planned as the initial therapy (transplant deferred). Some 395 patients with transplant-ineligible or transplant-deferred NDMM were randomly assigned to eight cycles of D-VRd or VRd followed by D-Rd or Rd until progression. The primary endpoint was overall minimal residual disease (MRD)-negativity rate at 10-5 by next-generation sequencing. Major secondary endpoints included complete response (CR) or better (≥CR) rate, progression-free survival and sustained MRD-negativity rate at 10-5. At a median follow-up of 58.7 months, the MRD-negativity rate was 60.9% with D-VRd versus 39.4% with VRd (odds ratio, 2.37; 95% confidence interval (CI), 1.58-3.55; P < 0.0001). Rates of ≥CR (81.2% versus 61.6%; P < 0.0001) and sustained MRD negativity (≥12 months; 48.7% versus 26.3%; P < 0.0001) were significantly higher with D-VRd versus VRd. Risk of progression or death was 43% lower for D-VRd versus VRd (hazard ratio, 0.57; 95% CI, 0.41-0.79; P = 0.0005). Adverse events were consistent with the known safety profiles for daratumumab and VRd. Combining daratumumab with VRd produced deeper and more durable MRD responses versus VRd alone. The present study supports D-VRd quadruplet therapy as a new standard of care for transplant-ineligible or transplant-deferred NDMM. ClinicalTrials.gov registration: NCT03652064 .

• MeSH
• Bortezomib * administration & dosage   adverse effects   therapeutic use   MeSH
• Dexamethasone * administration & dosage   adverse effects   therapeutic use   MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Lenalidomide * administration & dosage   adverse effects   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple Myeloma * drug therapy   diagnosis   mortality   pathology   MeSH
• Antibodies, Monoclonal * administration & dosage   adverse effects   therapeutic use   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   adverse effects   administration & dosage   MeSH
• Neoplasm, Residual MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

• MeSH
• Dexamethasone administration & dosage   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Fluorescein Angiography MeSH
• Fluprednisolone administration & dosage   MeSH
• Immunohistochemistry MeSH
• Iridectomy methods   MeSH
• Humans MeSH
• Melanoma * diagnostic imaging   pathology   MeSH
• Iris Neoplasms * surgery   diagnostic imaging   drug therapy   pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Dexamethasone administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Conjunctival Diseases diagnostic imaging   complications   pathology   MeSH
• Recurrence MeSH
• Scleritis * diagnostic imaging   etiology   pathology   MeSH
• Tuberculoma diagnosis   complications   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Acyclovir administration & dosage   MeSH
• Anti-Bacterial Agents administration & dosage   MeSH
• Dexamethasone administration & dosage   MeSH
• Endophthalmitis * diagnostic imaging   etiology   pathology   therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Ophthalmologic Surgical Procedures * adverse effects   MeSH
• Disease Progression MeSH
• Uveitis diagnosis   drug therapy   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Dexamethasone administration & dosage   MeSH
• Adult MeSH
• Ectopia Lentis diagnostic imaging   etiology   pathology   therapy   MeSH
• Carbonic Anhydrase Inhibitors administration & dosage   MeSH
• Humans MeSH
• Marfan Syndrome * diagnostic imaging   pathology   therapy   MeSH
• Ophthalmologic Surgical Procedures MeSH
• Tomography, Optical Coherence MeSH
• Corneal Topography MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH

• MeSH
• Dexamethasone administration & dosage   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• HLA-B27 Antigen * MeSH
• Humans MeSH
• Mydriatics therapeutic use   MeSH
• Uveitis, Anterior * drug therapy   pathology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH