Giant cell tumor of femur with single pulmonary metastasis - yet another curative oligometastasis.

ABSTRACT: Giant cell tumor of bone (GCT) is a benign tumor of bone that is known to be locally aggressive rarely metastasizing to distant sites, most commonly to the lungs. The reported pulmonary metastasis incidence is 1 - 9%. We report a case of GCT with solitary pulmonary metastasis who had significant clinical benefit and disease control with sequential application of surgical resection of pulmonary metastasis, local external beam radiation therapy (EBRT), and systemic Denosumab. We wish to highlight that even in metastatic GCT, there is significant clinical benefit in aggressive treatment.

Novel SmartReservoirs for hydrogel-forming microneedles to improve the transdermal delivery of rifampicin.

Hydrogel-forming microneedles (HF-MNs) are composed of unique cross-linked polymers that are devoid of the active pharmaceutical ingredient (API) within the microneedle array. Instead, the API is housed in a reservoir affixed on the top of the baseplate of the HF-MNs. To date, various types of drug-reservoirs and multiple solubility-enhancing approaches have been employed to deliver hydrophobic molecules combined with HF-MNs. These strategies are not without drawbacks, as they require multiple manufacturing steps, from solubility enhancement to reservoir production. However, this current study challenges this trend and focuses on the delivery of the hydrophobic antibiotic rifampicin using SmartFilm-technology as a solubility-enhancing strategy. In contrast to previous techniques, smart drug-reservoirs (SmartReservoirs) for hydrophobic compounds can be manufactured using a one step process. In this study, HF-MNs and three different concentrations of rifampicin SmartFilms (SFs) were produced. Following this, both HF-MNs and SFs were fully characterised regarding their physicochemical and mechanical properties, morphology, Raman surface mapping, the interaction with the cellulose matrix and maintenance of the loaded drug in the amorphous form. In addition, their drug loading and transdermal permeation efficacy were studied. The resulting SFs showed that the API was intact inside the cellulose matrix within the SFs, with the majority of the drug in the amorphous state. SFs alone demonstrated no transdermal penetration and less than 20 ± 4 µg of rifampicin deposited in the skin layers. In contrast, the transdermal permeation profile using SFs combined with HF-MNs (i.e. SmartReservoirs) demonstrated a 4-fold increase in rifampicin deposition (80 ± 7 µg) in the skin layers and a permeation of approx. 500 ± 22 µg. Results therefore illustrate that SFs can be viewed as novel drug-reservoirs (i.e. SmartReservoirs) for HF-MNs, achieving highly efficient loading and diffusion properties through the hydrogel matrix.

Cucumber-Derived Exosome-like Vesicles and PlantCrystals for Improved Dermal Drug Delivery.

(1) Background: Extracellular vesicles (EVs) are considered to be efficient nanocarriers for improved drug delivery and can be derived from mammalian or plant cells. Cucumber-derived EVs are not yet described in the literature. Therefore, the aim of this study was to produce and characterize cucumber-derived EVs and to investigate their suitability to improve the dermal penetration efficacy of a lipophilic active ingredient (AI) surrogate. (2) Methods: The EVs were obtained by classical EVs isolation methods and by high pressure homogenization (HPH). They were characterized regarding their physico-chemical and biopharmaceutical properties. (3) Results: Utilization of classical isolation and purification methods for EVs resulted in cucumber-derived EVs. Their dermal penetration efficacy for the AI surrogate was 2-fold higher when compared to a classical formulation and enabled a pronounced transdermal penetration into the viable dermis. HPH resulted in submicron sized particles composed of a mixture of disrupted plant cells. A successful isolation of pure EVs from this mixture was not possible with classical EVs isolation methods. The presence of EVs was, therefore, proven indirectly. For this, the lipophilic drug surrogate was admixed to the cucumber juice either prior to or after HPH. Admixing of the drug surrogate to the cucumber prior to the HPH resulted in a 1.5-fold increase in the dermal penetration efficacy, whereas the addition of the AI surrogate to the cucumber after HPH was not able to improve the penetration efficacy. (4) Conclusions: Results, therefore, indicate that HPH causes the formation of EVs in which AI can be incorporated. The formation of plant EVs by HPH was also indicated by zeta potential analysis.

Production and Characterization of Sumac PlantCrystals: Influence of High-Pressure Homogenization on Antioxidant Activity of Sumac (Rhus coriaria L.).

Oxidative stress diseases are usually treated or prevented by using antioxidants from natural or artificial sources. However, as a sustainable source of phytochemicals, plants got a renewed interest in obtaining their active agents using green extraction technologies, i.e., sustainable extraction techniques that reduce energy consumption, use renewable sources and result in less post-extraction wastes. The high-pressure homogenization (HPH) technique was introduced into the food industry since it was invented in 1900 to homogenize milk and later to produce fruit juices with a longer shelf-life without preservatives. Recently, HPH was introduced as an eco-friendly method to nanomill plants for improved extraction efficacy without using organic solvents. In this study, sumac was used as an antioxidants-rich spice model to investigate the effects of HPH on its antioxidant capacity (AOC). Sumac was rendered into PlantCrystals by using HPH. Particle size characterization proved the presence of submicron-sized particles (about 750 nm). Thus, HPH was able to produce sumac PlantCrystals and increased the AOC of bulk sumac by more than 650% according to the ORAC (oxygen radical absorbance capacity) assay. The polyphenol and flavonoid contents showed higher values after HPH. Interestingly, the DPPH (1,1-diphenyl-2-picrylhydrazyl) assay also showed a well improved AOC (similar to ascorbic acid) after HPH. In fact, in this study, the PlantCrystal-technology was demonstrated to cause an efficient cell rupture of the sumac plant cells. This caused an efficient release of antioxidants and resulted in sumac PlantCrystals with a 6.5-fold higher antioxidant capacity when compared to non-processed sumac bulk material.

Improved Antioxidant Capacity of Black Tea Waste Utilizing PlantCrystals.

Antioxidants are recommended to prevent and treat oxidative stress diseases. Plants are a balanced source of natural antioxidants, but the poor solubility of plant active molecules in aqueous media can be a problem for the formulation of pharmaceutical products. The potential of PlantCrystal technology is known to improve the extraction efficacy and antioxidant capacity (AOC) of different plants. However, it is not yet proved for plant waste. Black tea (BT) infusion is consumed worldwide and thus a huge amount of waste occurs as a result. Therefore, BT waste was recycled into PlantCrystals using small-scale bead milling. Their characteristics were compared with the bulk-materials and tea infusion, including particle size and antioxidant capacity (AOC) in-vitro. Waste PlantCrystals possessed a size of about 280 nm. Their AOC increased with decreasing size according to the DPPH (1,1-diphenyl-2-picrylhydrazyl) and ORAC (oxygen radical absorbance capacity) assays. The AOC of the waste increased about nine-fold upon nanonization, leading to a significantly higher AOC than the bulk-waste and showed no significant difference to the infusion and the used standard according to DPPH assay. Based on the results, it is confirmed that the PlantCrystal technology represents a natural, cost-effective plant-waste recycling method and presents an alternative source of antioxidant phenolic compounds.

PlantCrystals-Nanosized Plant Material for Improved Bioefficacy of Medical Plants.

PlantCrystals are obtained by milling plant material to sizes <10 µm. Due to the disruption of the plant cells, active compounds are easily released, rendering the PlantCrystal technology an effective and low-cost process for the production of environmentally friendly plant extracts. The extracts can be used to produce phytomedicines, nutritional supplements or cosmetic products. Previous studies could already demonstrate the use of PlantCrystals to improve the antimicrobial or antifungal activity of different plants. This study investigated whether PlantCrystal technology is suitable to produce plant derived formulations with high antioxidant capacity. The study also aimed to identify the most suitable production methods for this. METHODS: Various plant materials and parts of plants, i.e., seeds, leaves and flowers, and different methods were employed for the production. PlantCrystals were characterized regarding size, physical stability and antioxidant capacity (AOC). RESULTS: PlantCrystals with particles <1 µm were produced from the different plant materials. Both production methods, i.e., high-pressure homogenization, bead milling or the combination of both were suitable to obtain PlantCrystals. Nano milling of the plant material greatly affected their AOC and resulted in formulations with distinctly higher AOC when compared to classical extracts. CONCLUSIONS: Rendering plant material into small sized particles is highly effective to obtain plant extracts with high biological efficacy.

Multiple Extramedullary Plasmacytoma in a Setting of Complete Bone Marrow Remission: Food for Thought.

Extramedullary plasmacytoma as a mode of relapse in multiple myeloma (MM) is unusual. Current recommendations do not incorporate the routine use of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) imaging prior to haematopoietic stem cell transplant (HSCT) in MM. We report a case of relapsed MM with complete remission as per IMWG criteria. In the interim period, before the HSCT, the patient had localizing neurological signs and symptoms attributed to multiple extramedullary plasmacytomas. The uniqueness of this case is that this patient after complete marrow remission with no obvious external masses had unexpected, symptomatic multiple extramedullary plasmacytomas. This case illustrates the need for integration of FDG PET/CT imaging into routine pre-HSCT investigations in relapsed MM to prevent missing any asymptomatic extramedullary plasmacytomas.

Demographics, Clinical Characteristics, Management, and Outcomes of Acute Heart Failure Patients: Observations from the Oman Acute Heart Failure Registry.

OBJECTIVES: We sought to describe the demographics, clinical characteristics, management and outcomes of patients in Oman with acute heart failure (AHF) as part of the Gulf aCute heArt failuRe rEgistry (CARE) project. METHODS: Data were analyzed from 988 consecutive patients admitted with AHF to 12 hospitals in Oman between 14 February and 14 November 2012. RESULTS: The mean age of our patients was 63±12 years. Over half (57%) were male and 95% were Omani citizens. Fifty-seven percent of patients presented with acute decompensated chronic heart failure (ADCHF) while 43% had new-onset AHF. The primary comorbid conditions were hypertension (72%), coronary artery disease (55%), and diabetes mellitus (53%). Ischemic heart disease (IHD), hypertensive heart disease, and idiopathic cardiomyopathy were the most common etiologies of AHF in Oman. The median left ventricular ejection fraction of the cohort was 36% (27-45%) with 56% of the patients having heart failure with reduced ejection fraction (< 40%). Atrial fibrillation was seen in 15% of patients. Acute coronary syndrome (ACS) and non-compliance with medications were the most common precipitating factors. At discharge, angiotensin converting enzyme inhibitors and beta-blockers were prescribed adequately, but aldosterone antagonists were under prescribed. Within 12-months follow-up, one in two patients were rehospitalized for AHF. In-hospital mortality was 7.1%, which doubled to 15.7% at three months and reached 26.4% at one-year post discharge. CONCLUSIONS: Oman CARE was the first prospective multicenter registry of AHF in Oman and showed that heart failure (HF) patients present at a younger age with recurrent ADCHF and HF with reduced ejection fraction. IHD was the most common etiology of HF with a low prevalence of AHF, but a high prevalence of acute coronary syndrome and non-compliance with medications precipitating HF. A quarter of patients died at one-year follow-up even though at discharge medical therapy was nearly optimal. Our study indicates an urgent need for prevention, early diagnosis, and treatment of AHF in Oman.

Fatal Renal Failure in a Spinal Cord Injury Patient with Vesicoureteric Reflux Who Underwent Repeated Ureteric Reimplantations Unsuccessfully: Treatment Should Focus on Abolition of High Intravesical Pressures rather than Surgical Correction of Reflux.

A 29-year-old man developed paraplegia at T-10 level due to road traffic accident in 1972. Both kidneys were normal and showed good function on intravenous urography. Division of external urethral sphincter was performed in 1973. In 1974, cystogram showed retrograde filling of left renal tract, which was hydronephrotic. Left ureteric reimplantation was performed. Following surgery, cystogram revealed marked retrograde filling of left renal tract as before. Penile sheath drainage was continued. In 1981, intravenous urography revealed bilateral severe hydronephrosis. Left ureteric reimplantation was performed again in 1983. Blood pressure was 220/140 mm Hg; this patient was prescribed atenolol. Cystogram showed gross left vesicoureteral reflux. Intermittent catheterisation was commenced in 2001. In 2007, proteinuria was 860 mg/day. This patient developed progressive renal failure and expired in 2012. In a spinal cord injury patient with vesicoureteral reflux, the treatment should focus on abolition of high intravesical pressures rather than surgical correction of vesicoureteric reflux. Detrusor hyperactivity and high intravesical pressures are the basic causes for vesicoureteral reflux in spinal cord injury patients. Therefore, it is important to manage spinal cord injury patients with neuropathic bladder by intermittent catheterisations along with antimuscarinic drug therapy in order to abolish high detrusor pressures and prevent vesicoureteral reflux. Angiotensin-converting enzyme inhibitors or angiotensin-receptor-blocking agents should be prescribed even in the absence of hypertension when a spinal cord injury patient develops vesicoureteral reflux and proteinuria.

Epidemiology of systemic mycoses among renal-transplant recipients in India.

BACKGROUND: Systemic mycoses have a high impact on tropical renal-transplant recipients. METHODS: Data from 1,476 primary renal-transplant recipients was prospectively recorded from 1986 to 2000 at a single center. Cumulative incidence of systemic mycoses, its time of occurrence, risk factors, outcome, and postmortem findings in 30 patients with systemic mycoses were analyzed. RESULTS: A total of 110 episodes of systemic mycoses occurred in 98 patients. The fungal genera Aspergillus, Cryptococcus, and Candida constituted 61% of pathogens, 45% localizing to the lungs. Cytomegalovirus (CMV) disease caused a 5-fold and chronic liver disease a 2-fold increase in systemic mycoses. Tuberculosis (TB) with or without nocardiosis was a significant coinfection. Cyclosporine (CsA) was associated with nearly a 4-fold risk of systemic mycoses less than 6 months from the time of transplantation as compared with prednisolone+azathioprine (PRED+AZA) therapy. Overall, the probability of survival with systemic mycoses was 73.4%, 60.8%, 39.5%, and 25.6% and was 92.5%, 87.5%, 80.0%, and 75.5% without systemic mycoses at 1, 2, 5, and 10 years, respectively (P<0.0001). An extended Cox model with time-independent and dependent covariates showed greater than 15 times the risk of death among those who develop systemic mycoses. Similarly, Posttransplantation (postTX) TB+/-Nocardiosis, preTX TB, CMV disease, diabetes mellitus, PTDM, chronic liver disease (>40 months), and Pred+AZA immunosuppression (>2 years) had 3.5, 1.5, 2.9, 1.9, 1.4, 1.6, 2.3 times the risk for death, respectively, as compared with those who did not have those risk factors. CONCLUSIONS: There is a recent predominance of Aspergillus among the transplant recipients. The risk factors for systemic mycoses are CMV disease, chronic liver disease, and hyperglycemia, and TB is an important coinfection. Systemic mycoses increased in the early postTX period with CsA. The risk factors for death are systemic mycoses, CMV disease, chronic liver disease (>40 months), diabetes mellitus, and Pred+AZA immunosuppression (>2 years). Overall, the probability of survival with systemic mycoses was poor; however, survival has recently improved.

Reflujo gastroesofagico en niños / Gastroesophageal reflux in children

Los autores, de este trabajo de la Unidad en Nutrición y Gastroenterología Pediátrica, del Hospital Miguel Pérez Carreño (IVSS), enfocan en este estudio el reflujo gastroesofágico e indican que le va a corresponder alpediatra decidir en que momento, va a ser referido el paciente a un especialistapara estudios especiales. Los diagnósticos con que se encuentran son variados y cada una de ellos tiene un lugar especial en el diagnóstico y tratamiento de la enfermedad