Radiation therapy is not only a mainstay in the treatment of many malignancies but also results in collateral obliteration of microvasculature and dermal/subcutaneous fibrosis. Soft tissue ...reconstruction of hypovascular, irradiated recipient sites through fat grafting remains challenging; however, a coincident improvement in surrounding skin quality has been noted. Cell-assisted lipotransfer (CAL), the enrichment of fat with additional adipose-derived stem cells (ASCs) from the stromal vascular fraction, has been shown to improve fat volume retention, and enhanced outcomes may also be achieved with CAL at irradiated sites. Supplementing fat grafts with additional ASCs may also augment the regenerative effect on radiation-damaged skin. In this study, we demonstrate the ability for CAL to enhance fat graft volume retention when placed beneath the irradiated scalps of immunocompromised mice. Histologic metrics of fat graft survival were also appreciated, with improved structural qualities and vascularity. Finally, rehabilitation of radiation-induced soft tissue changes were also noted, as enhanced amelioration of dermal thickness, collagen content, skin vascularity, and biomechanical measures were all observed with CAL compared to unsupplemented fat grafts. Supplementation of fat grafts with ASCs therefore shows promise for reconstruction of complex soft tissue defects following adjuvant radiotherapy.
•Solid organ transplantation is a well-recognized risk factor for aspergillosis.•Diagnosis is often challenging, especially in the comorbid patient.•Voriconazole is the first-line antifungal ...agent.•Prompt therapy and removal of infected tissue where possible are essential.•The prognosis for invasive Aspergillus is extremely poor.
A renal transplant recipient aged 68 years experienced multiple complications after an initial good graft function from a deceased donor transplant. Late in the first week, the patient was oliguric with hematuria; the graft failed in week 2 after the development of a hematoma from a rupture of a renal artery aneurysm. He had a recurrent bleed from the internal iliac graft site and subsequently developed painful dark patches on his leg, distal to where the transplant had been. Histology from the explanted graft and skin biopsies demonstrated Aspergillus flavus; this was also grown in the culture of the external iliac artery tissue. Systemic aspergillosis is rare but well recognized, especially in the immunocompromised. Presentations include mycotic aneurysms and secondary cutaneous aspergillosis from hematogenous spread. Diagnosis requires confirmation by histology or direct culture, but a high β-glucan concentration and positive galactomannan antigen can suggest invasive fungal infection in the early stages of the disease. Cases should be managed with systemic antifungals and involvement of local microbiology services; unfortunately, the prognosis is poor.
Sodium intake is correlated with the development of hypertension. Guyton's principals suggest that the 24-hour urinary sodium excretion reflects sodium ingestion over the same period. 24-hour urine ...collections are arduous to collect, so many centers use spot urinary measurements instead. We compared spot to matched 24-hour urinary electrolyte measurements.
We examined 419 hypertensive patients from the UCL Complex Hypertension Clinic. 77 had matched and complete 24-hour and spot urinary and serum biochemistry to examine.We compared the spot and 24-hour urinary; sodium concentration, Na/Cr ratio, FENa, Kawasaki and Tanaka estimated sodium excretion as well as the potassium concentration, K/Cr ratio, Kawasaki and Tanaka potassium excretion.
Our cohort was 58% male and the median age was 41 years. The 24-hour and spot Na concentrations correlated moderately (r = 0.4633, P < 0.0001). The 24-hour and spot Na/creatinine ratios correlated weakly (r = 0.2625, P = 0.0194). The 24-hour and spot FENa results showed a weak negative correlation (r = -0.222, P = ns). The 24-hour sodium excretion and the Kawasaki-derived spot urine sodium excretion correlated moderately (r = 0.3118, P = 0.0052). All Bland-Altman analyses showed poor agreement.The 24-hour and spot potassium concentrations correlated very poorly (r = 0.1158, P = ns). The 24-hour and spot urinary K/creatinine ratios correlated weakly (r = 0.47, P ≤ 0.0001). 24-hour and Kawasaki and Tanaka estimated potassium excretions correlated much better (r = 0.58, P < 0.0001).
Spot urinary measurements of sodium give a very poor understanding of the natriuresis occurring over the same 24-hour period. The Kawasaki and Tanaka estimations of the 24-hour sodium excretion showed a much lower correlation than previously reported.
An invaluable part of the plastic surgeon's technical arsenal for soft tissue contouring, fat grafting continues to be plagued by unpredictable outcomes, resulting in either reoperation and/or ...patient dissatisfaction. Thus, extensive research has been conducted into the effects of adipose tissue procurement, processing, and placement on fat graft quality at both the cellular level and in terms of overall volume retention. Herein, we present an overview of the vast body of literature in these areas, with additional discussion of cell-assisted lipotransfer as a therapy to improve volume retention, and on the controversial use of autologous fat in the setting of prior irradiation.
A 58-year-old man, who after reporting several days of abdominal pain was found to have acute kidney injury, was transferred to our unit from a regional hospital. Laboratory investigations confirmed ...acute kidney injury—his serum creatinine concentration was 703 μmol/L with preserved urinary output; his remaining serum biochemistry was unremarkable. Non-obstructive kidney stones of less than 15 mm can be treated conservatively and monitored closely; an increase in the size of the stone or complications, such as infections, may result in a more proactive approach.
...by March 2020 our hospital had rapidly built a “pod” in its car park for the expected small number of cases of SARS-CoV-2 infection who would be tested and managed without risk to other hospital ...patients and staff. Back in 2005, it was already known that the spike protein of coronavirus causing SARS (severe ARDS), SARS-CoV-1, bound to the angiotensin-converting enzyme 2 (ACE2) to gain entry to infect cells 1, and this contributes to the lung injury seen 2. Knowing this, there has been a theoretical concern that patients treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) may be less or more susceptible to viral infection: ...patients with COVID-19 and AKI had a higher mortality than non-COVID-19 critically ill patients with AKI.
Mutations in BRCA1 and BRCA2 (BRCA1/2), components of the homologous recombination DNA repair (HRR) pathway, are associated with hereditary breast and ovarian cancers. Poly(ADP-ribose) polymerase ...(PARP) inhibitors are selectively cytotoxic to animal cells with defective HRR, but results in human cancer cells have been contradictory. We undertook, to our knowledge, the first comprehensive in vitro and in vivo investigations of the antitumor activity of the PARP inhibitor AG014699 in human cancer cells carrying mutated or epigenetically silenced BRCA1/2.
We used nine human cell lines, four with nonmutated BRCA1/2 (MCF7, MDA-MB-231, and HCC1937-BRCA1 breast cancer and OSEC-2 ovarian surface epithelial), two with mutated BRCA1 (MDA-MB-436 and HCC1937 breast cancer), one with mutated BRCA2 (CAPAN-1 pancreatic cancer), one that was heterozygous for BRCA2 (OSEC-1 ovarian surface epithelial), and one with epigenetically silenced BRCA1 (UACC3199 breast cancer), and two Chinese hamster ovary cell lines, parental AA8 and XRCC3 mutated IRS 1SF. We assessed cytotoxicity, DNA damage, and HRR function. Antitumor activity of AG014699 was determined by growth of xenograft tumors (five mice per treatment group). Long-term safety of AG014699 was assessed.
AG014699 (≤10 μM) was cytotoxic to cells with mutated BRCA1/2 or XRCC3 and to UACC3199 cells with epigenetically silenced BRCA1 but not to cells without BRCA1/2 or XRCC3 mutations or that were heterozygous for BRCA2 mutation. AG014699 induced DNA double-strand breaks in all nine cell lines studied. HRR was observed only in cells with functional BRCA1/2 proteins. Growth of xenograft tumors with BRCA1/2 mutations or with epigenetically silenced BRCA1 was reduced by AG014699 treatment, and combination treatment with AG014699 plus carboplatin was more effective than either drug alone. AG014699 was not toxic in mice with nonmutated or heterozygous BRCA2.
Human cancer cells or xenograft tumors with mutated or epigenetically silenced BRCA1/2 were sensitive to AG014699 monotherapy, indicating a potential role for PARP inhibitors in sporadic human cancers.
Cell-assisted lipotransfer has shown much promise as a technique for improving fat graft take. However, the concentration of stromal vascular fraction cells required to optimally enhance fat graft ...retention remains unknown.
Human lipoaspirate was processed for both fat transfer and harvest of stromal vascular fraction cells. Cells were then mixed back with fat at varying concentrations ranging from 10,000 to 10 million cells per 200 μl of fat. Fat graft volume retention was assessed by means of computed tomographic scanning over 8 weeks, and then fat grafts were explanted and compared histologically for overall architecture and vascularity.
Maximum fat graft retention was seen at a concentration of 10,000 cells per 200 μl of fat. The addition of higher number of cells negatively impacted fat graft retention, with supplementation of 10 million cells producing the lowest final volumes, lower than fat alone. Interestingly, fat grafts supplemented with 10,000 cells showed significantly increased vascularity and decreased inflammation, whereas fat grafts supplemented with 10 million cells showed significant lipodegeneration compared with fat alone
: The authors' study demonstrates dose dependence in the number of stromal vascular fraction cells that can be added to a fat graft to enhance retention. Although cell-assisted lipotransfer may help promote graft survival, this effect may need to be balanced with the increased metabolic load of added cells that may compete with adipocytes for nutrients during the postgraft period.
ABSTRACT X-linked proximal tubulopathies are rare diseases that predominantly affect men. Women are generally carriers and clinical or biochemical manifestations are usually absent or mild. We ...present the case of a young woman who presented with a full phenotype of Dent disease type 1 due to a de novo mutation in the CLCN5 gene and a skewed X-chromosome inactivation. Although cases of overt Dent disease type 2 and Lowe syndrome in women have been described in the literature, to our knowledge this is the first case of overt Dent disease type 1.
Stem Cells in Bone Regeneration Walmsley, Graham G.; Ransom, Ryan C.; Zielins, Elizabeth R. ...
Stem cell reviews,
10/2016, Letnik:
12, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Bone has the capacity to regenerate and repair itself. However, this capacity may be impaired or lost depending on the size of the defect or the presence of certain disease states. In this review, we ...discuss the key principles underlying bone healing, efforts to characterize bone stem and progenitor cell populations, and the current status of translational and clinical studies in cell-based bone tissue engineering. Though barriers to clinical implementation still exist, the application of stem and progenitor cell populations to bone engineering strategies has the potential to profoundly impact regenerative medicine.
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