Mcdougallsilver2832

Aim To evaluate, in Systemic sclerosis (SSc) patients, the body composition and the bone status according to the peripheral microcirculatory condition, assessed and scored by nailfold videocapillaroscopy (NVC, "Early", "Active", "Late" patterns). Methods Body composition and bone mineral density (BMD) were assessed by Dual X-ray absorptiometry and dedicated software (GE Lunar USA) in 37 female SSc patients classified according to the 2013 EULAR/ACR criteria and 40 sex-matched healthy subjects. Clinical, laboratory, body composition and bone parameters were analyzed according to the different NVC patterns. Means were compared by the Student's t test or one-way analysis of variance; medians were compared by the Kruskal-Wallis test; and frequencies by the chi-square test. Results Higher prevalence of vertebral (21% vs 7%) and femoral (35% vs 7%) osteoporosis (OP) was found in SSc. Particularly SSc patients with "Late" NVC pattern showed a significantly higher prevalence of vertebral (p = 0.018) and femoral OP (p = 0.016). Regional assessment of bone mass (BM) in seven different body areas showed a significantly lower BMD only at the total spine (p = 0.008) and femoral neck (p = 0.027) in advanced microvascular damage. Patients with "Late" NVC pattern showed a lower whole-body lean mass (LM) compared to "Early" and "Active" NVC patterns, particularly at upper limbs. To note, in all body sites, BMD correlates with LM and BMC according to NVC pattern severity. Conclusions SSc patients with most severe microvascular damage show a significantly altered body composition and bone status suggesting a strong link between microvascular failure and associated muscle/bone sufferance.Purpose Ipilimumab, a monoclonal antibody inhibiting CLTA-4, is an established treatment in metastatic melanoma, either alone or in combination with nivolumab, and results in immune mediated adverse events, including endocrinopathy. Hypophysitis is one of the most common endocrine abnormalities. An early recognition of hypophysitis may prevent life threatening consequences of hypopituitarism; therefore, biomarkers to predict which patients will develop hypophysitis would have clinical utility. Recent studies suggested that a decline in TSH may serve as an early marker of IH. This study was aimed at assessing the utility of thyroid function tests in predicting development of hypophysitis. Methods A retrospective cohort study was performed for all patients (n = 308) treated with ipilimumab either as a monotherapy or in combination with nivolumab for advanced melanoma at the Royal Marsden Hospital from 2010 to 2016. Thyroid function tests, other pituitary function tests and Pituitary MRIs were used to identify those with hypophysitis. Results and conclusions Ipilimumab-induced hypophysitis (IH) was diagnosed in 25 patients (8.15%). A decline in TSH was observed in hypophysitis cohort during the first three cycles but it did not reach statistical significance (P = 0.053). A significant fall in FT4 (P less then 0.001), TSH index (P less then 0.001) and standardised TSH index (P less then 0.001) prior to cycles 3 and 4 in hypophysitis cohort was observed. TSH is not useful in predicting development of IH. FT4, TSH index and standardised TSH index may be valuable but a high index of clinical suspicion remains paramount in early detection of hypophysitis.Background A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. Objective The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. Methods The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. Results At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. Conclusions This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.Despite the threat of Fusarium dieback posed due to ambrosia fungi cultured by ambrosia beetles such as Euwallacea spp., the wood-degradation mechanisms utilized by ambrosia fungi are not fully understood. In this study, we analyzed the 16S rRNA and 18S rRNA genes of the microbial community from the Ficus tree tunnel excavated by Euwallacea interjectus and isolated the cellulose-degrading fungus, Fusarium spp. strain EI, by enrichment culture with carboxymethyl cellulose as the sole carbon source. The cellulolytic enzyme secreted by the fungus was identified and expressed in Pichia pastoris, and its enzymatic properties were characterized. The cellulolytic enzyme, termed FsXEG12A, could hydrolyze carboxymethyl cellulose, microcrystalline cellulose, xyloglucan, lichenan, and glucomannan, indicating that the broad substrate specificity of FsXEG12A could be beneficial for degrading complex wood components such as cellulose, xyloglucan, and galactoglucomannan in angiosperms. Inhibition of FsXEG12A function is, thus, an effective target for Fusarium dieback caused by Euwallacea spp.Portal vein aneurysms are rare vascular findings for which there are no optimal treatment guidelines. The scarce knowledge about their etiology, natural history, and management mean that there are limited treatment options. Here, we describe the case of a 69-year-old woman who presented with a 35-mm hypoechoic area in the hilar region of the liver that was accidentally detected by ultrasonography. Color Doppler ultrasonography demonstrated a mass with internal flow contiguous with portal vein, which was confirmed to be a portal vein aneurysm by computed tomography. Given that she experienced no symptoms of impending rupture or thrombosed aneurysms, we adopted a conservative treatment. Follow-up imaging demonstrated slow progression of the aneurysm diameter, from 35 to 43 mm at 3 years, and to 48 mm at 6 years; subsequent imaging after 6 years did not show any change in the diameter from 48 mm. However, the portal vein aneurysm completely regressed with no complications at a follow-up of over 10 years. This case suggests that long-term observation with periodic imaging may be an acceptable therapeutic option for asymptomatic portal vein aneurysms that show no short-term improvement. This case report contributes to a better understanding of how to treat this rare disease.Aortoesophageal fistula (AEF) is a highly life-threatening condition, even when treated promptly. However, little is known about the treatment for AEF in patients with advanced esophageal cancer. We report the case of a 69-year-old man diagnosed with esophageal squamous cell carcinoma (ESCC) that was admitted to our hospital for ESCC treatment. On diagnosis of unresectable ESCC invading the thoracic aorta, chemotherapy was administered. The response to treatment after two courses was evaluated as stable disease. We performed radiation therapy followed by bypass operation for esophageal stenosis. After radiation therapy, AEF was detected. His condition improved after hemostasis using thoracic endovascular aortic repair (TEVAR). He was discharged from our care after treatment with antibiotics; he died due to cancer progression 7 months after TEVAR. AEF with ESCC is a lethal condition that may occur during cancer treatment; however, TEVAR might help improve the patient's condition.Proniosomes are free-flowing systems with coating carriers, which developed as a method for improving the drug flow and pulmonary delivery. Extensive research on proniosomes was done to enhance the dry powder inhalers (DPI)'s inhalation performance. This research aimed at studying the impact of lactose-mannitol mixture additives on the proniosome's physicochemical properties as a method for improving the inhalation efficiency of DPI. Vismodegib has been employed as a compound model. Box-Behnken design has been employed to prepare different proniosomes formulae by incorporating various (A) span 60 concentrations, (B) lactose concentrations and (C) mannitol total carrier mixture. The measured responses were vesicle size (R1), %release (R2), Carr's index (R3) and %recovery (R4). The results displayed that R1 and R4 were significantly antagonistic to C and significantly synergistic to both A and B while R2 and R3 were significantly synergistic to C and significantly antagonistic to both A and B. The optimal formula was selected for its aerodynamic behaviour, cytotoxic activity and bioavailability assessment. The optimal formula resulted in better Vismodegib lung deposition, cytotoxic activity and relative bioavailability. This novel formula could be a promising carrier for sustained delivery of drugs via the pulmonary route.Background PSMA-targeted radioligand therapy (PSMA-RLT) yielded impressive results in the metastasized castration-resistant prostate carcinoma (mCRPC) setting. High expression of PSMA is essential for successful PSMA-RLT. However, some patients develop [18F]FDG-avid lesions with low or no PSMA expression ([18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings on PET/CT) in the course of treatment. Those lesions are not affected by PSMA-RLT and a change in therapy management is needed. To enable early mismatch detection, possible blood parameters as indicators for the occurrence of [18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings on PET/CT were evaluated. Methods Retrospective study of N = 66 advanced mCRPC patients with dual [68Ga]Ga-PSMA-11 and [18F]FDG PET/CT imaging within 4 weeks, who were referred for or received [177Lu]Lu-PSMA-617 radioligand therapy. Prostate-specific antigen (PSA), neuron-specific enolase (NSE), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP) were tested as indicators for the occurren An introduced scoring system of both parameters achieved a sensitivity of 90% and a specificity of 88% for the occurrence of [18F]FDG/[68Ga]Ga-PSMA-11 mismatch. Bozitinib Conclusion We observed a significantly higher absolute serum concentration and a higher relative increase of NSE in advanced mCRPC patients with [18F]FDG-avid and insufficient PSMA expressing metastases ([18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings on PET/CT) in our cohort. NSE might be used as a potential laboratory indicator for [18F]FDG/[68Ga]Ga-PSMA-11 mismatch findings, if this observation is confirmed in future, ideally prospective, studies in larger patient cohorts.