Fluoropolymer-MOF Hybrids with Switchable Hydrophilicity for 19F MRI-Monitored Cancer Therapy.

Cancer theranostics that combines cancer diagnosis and therapy is a promising approach for personalized cancer treatment. However, current theranostic strategies suffer from low imaging sensitivity for visualization and an inability to target the diseased tissue site with high specificity, thus hindering their translation to the clinic. In this study, we have developed a tumor microenvironment-responsive hybrid theranostic agent by grafting water-soluble, low-fouling fluoropolymers to pH-responsive zeolitic imidazolate framework-8 (ZIF-8) nanoparticles by surface-initiated RAFT polymerization. The conjugation of the fluoropolymers to ZIF-8 nanoparticles not only allows sensitive in vivo visualization of the nanoparticles by 19F MRI but also significantly prolongs their circulation time in the bloodstream, resulting in improved delivery efficiency to tumor tissue. The ZIF-8-fluoropolymer nanoparticles can respond to the acidic tumor microenvironment, leading to progressive degradation of the nanoparticles and release of zinc ions as well as encapsulated anticancer drugs. The zinc ions released from the ZIF-8 can further coordinate to the fluoropolymers to switch the hydrophilicity and reverse the surface charge of the nanoparticles. This transition in hydrophilicity and surface charge of the polymeric coating can reduce the "stealth-like" nature of the agent and enhance specific uptake by cancer cells. Hence, these hybrid nanoparticles represent intelligent theranostics with highly sensitive imaging capability, significantly prolonged blood circulation time, greatly improved accumulation within the tumor tissue, and enhanced anticancer therapeutic efficiency.

A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy.

Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate personalized nanovaccines based on a cationic fluoropolymer for post-surgical cancer immunotherapy. Nanoparticles formed by mixing the fluoropolymer with a model antigen ovalbumin, induce dendritic cell maturation via the Toll-like receptor 4 (TLR4)-mediated signalling pathway, and promote antigen transportation into the cytosol of dendritic cells, which leads to an effective antigen cross-presentation. Such a nanovaccine inhibits established ovalbumin-expressing B16-OVA melanoma. More importantly, a mix of the fluoropolymer with cell membranes from resected autologous primary tumours synergizes with checkpoint blockade therapy to inhibit post-surgical tumour recurrence and metastases in two subcutaneous tumour models and an orthotopic breast cancer tumour. Furthermore, in the orthotopic tumour model, we observed a strong immune memory against tumour rechallenge. Our work offers a simple and general strategy for the preparation of personalized cancer vaccines to prevent post-operative cancer recurrence and metastasis.

Surgical outcome of pulmonary artery reconstruction using the expanded polytetrafluoroethylene patch in patients with lung cancer.

PURPOSE: Pulmonary artery reconstruction is sometimes utilized as an alternative to pneumonectomy in lung cancer surgery. We herein report our experience of pulmonary artery reconstruction using an expanded polytetrafluoroethylene (ePTFE) patch based on the surgical results and long-term outcome. METHODS: Clinical records of lung cancer patients who underwent patch plasty were reviewed retrospectively. RESULTS: Between 2003 and 2017, pulmonary artery patch plasty were performed in 21 patients [18 males, 3 females; mean age 65 (range 47-79) years]. Induction chemoradiotherapy was performed in three patients. Bronchoplasty was performed in five patients. The pathologic stages were stage I in 3 patients, stage II in 6 and stage III in 12. Pneumonectomy, lobectomy and segmentectomy were performed in 2, 18 and 1 patient, respectively. The left upper lobe was the most frequent origin of lung cancer (15 patients). There was no reconstruction-related morbidity or mortality. The overall survival rate at 5 years was 64.1% with a mean follow-up of 39.5 months, and the survival rates for N0-1 and N2-3 were 80.8% and 28.6%, respectively. CONCLUSION: Patch angioplasty using the ePTFE sheet is a reliable procedure in radical surgery for lung cancer.

Low molecular weight PEI-based fluorinated polymers for efficient gene delivery.

Fluorinated biomaterials have been reported to have promising features as non-viral gene carriers. In this study, a series of fluorinated polymeric gene carriers were synthesized via Michael addition from low molecular weight polyethyleneimine (PEI) and fluorobenzoic acids (FBAs)-based linking compounds with different numbers of fluorine atoms. The structure-activity relationship (SAR) of these materials was systematically investigated. SAR studies showed that fluorine could screen the positive charge of these polymers. However, this shielding effect of fluorine would endow fluorinated polymers with good balance between DNA condensation and release. In vitro transfection results suggested that these fluorinated polymers could mediate efficient gene delivery. Flow cytometry and confocal microscopy studies demonstrated that more efficient cell uptake could be achieved by fluorinated materials with more fluorine atoms. Cytotoxicity assays showed that these fluorinated materials exhibited very low cytotoxicity even at high mass ratios. This study demonstrates that FBA-based fluorinated biopolymers have the potential for practical application.

Experiences with a temporary synthetic skin substitute after decompressive craniectomy: a retrospective two-center analysis.

BACKGROUND: Decompressive craniectomy is a commonly performed procedure. It reduces intracranial pressure, improves survival, and thus might have a positive impact on several neurosurgical diseases and emergencies. Sometimes primary skin closure is not possible due to cerebral herniation or extensive skin defects. In order to prevent further restriction of the underlying tissue, a temporary skin expansion might be necessary. METHODS AND MATERIAL: We retrospectively reviewed patients in need for a temporary skin substitute because skin closure was not possible after craniectomy without violating brain tissue underneath in a time period of 6 years (2011-2016). With this study, we present initial experiences of Epigard (Biovision, Germany) as an artificial temporary skin replacement. We performed this analysis at two level-1 trauma centers (Trauma Center Murnau, Germany; University Hospital of St. Poelten, Austria). Demographic data, injury and surgical characteristics, and complication rates were analyzed via chart review. We identified nine patients within our study period. Six patients suffered from severe traumatic brain injury and developed pronounced cerebral herniation in the acute or subacute phase. Three patients presented with non-traumatic conditions (one atypical intracerebral hemorrhage and two patients with extensive destructive tumors invading the skull and scalp). RESULTS: A total of 20 Epigard exchanges (range 1-4) were necessary before skin closure was possible. A CSF fistula due to a leaky Epigard at the interface to the skin was observed in two patients (22%). Additional complications were four wound infections, three CNS infections, and three patients developed a shunt dependency. Three patients died within the first month after injury. CONCLUSIONS: Temporary skin closure with Epigard as a substitute is feasible for a variety of neurosurgical conditions. The high complication and mortality rate reflect the complexity of the encountered pathologies and need to be considered when counseling the patient and their families.

Hyperbaric oxygen therapy in the treatment of diabetic foot ulcers--prudent or problematic: a case report.

Hyperbaric oxygen (HBO) therapy is increasingly used in the management of problem wounds, notably diabetic foot ulcers. However, concerns about unnecessary, inappropriate, and prolonged use of this adjunctive treatment exist. A case report of a 52-year-old patient with diabetes mellitus, Charcot foot, and a nonhealing plantar ulcer who had received HBO treatments only illustrates these concerns. He presented with normal pedal pulses, adequate transcutaneous partial oxygen pressure levels, no offloading footwear, and a heavily contaminated ulcer (Pseudomonas spp.). Following a course of oral antibiotics, appropriate topical wound care, and offloading instructions, the wound healed within 3 months. Advanced wound therapy modalities are only indicated for use in patients when accepted standards of wound care, including identification and correction of underlying disorders and comorbidities, have failed. To prevent misuse/overuse of HBO therapy, stand-alone HBO centers should include a multidisciplinary wound care team.

Polytetrafluoroethylene and bovine mesenterial vein grafts for hemodialysis access: a comparative study.

PURPOSE: This study aimed to evaluate the safety and patency rate of bovine mesenterial vein grafts (BMVG) for vascular access (VA) in hemodialysis patients (HDP), compared to expanded polytetrafluorethylene (ePTFE grafts) over a mid- to long-term period. METHODS: Patency and complication rate of 23 consecutive HDP with BMVG for VA were compared to a control group consisting of 23 similar HDP with ePTFE grafts. In both groups, the graft was placed preferably in a forearm loop configuration. The same surgeon performed all procedures. All patients were followed over a period of 4 yrs. RESULTS: Graft placement was successful in all patients. Patency rates did not differ significantly in both groups. However, there were less severe complications in the BMVG group. CONCLUSION: The BMVG is a viable alternative for HD access in patients where autologous construction is not possible, and should be given priority in patients with a failed ePTFE graft or high risk for infection.

Fluoropolymer coated Dacron or polytetrafluoroethylene for femoropopliteal bypass grafting: a multicentre trial.

BACKGROUND: This trial was designed to compare graft patency between expanded polytetrafluoroethylene (PTFE) and fluoro-polymer coated Dacron for femoropopliteal bypass in patients in whom saphenous vein was unavailable. METHODS: A multicentre prospective trial randomized 129 patients (74 men, 55 women) who underwent femoropopliteal bypass using either a PTFE or fluoropolymer coated Dacron graft. The indication for operation was disabling claudication in 68 (52.7%) and critical limb ischaemia in 61 (47.3%) patients. Distal anastomosis was above the knee in 76 (58.9%) and below the knee in 53 (41.1%) patients. RESULTS: Primary patency at 6, 12 and 24 months was 71%, 56% and 47% for PTFE and 50%, 36% and 36% for fluoropolymer coated Dacron (P = 0.002), respectively. Secondary patency at 6, 12 and 24 months was 77%, 60% and 48% for PTFE and 66%, 49% and 46% for fluoropolymer coated Dacron (P = 0.13), respectively. The superior primary patency of PTFE over fluoropolymer coated Dacron was most evident in patients with poor prognostic indicators for graft survival: critical limb ischaemia (P = 0.001); below-knee anastomosis (P = 0.01); and smaller (6 mm) diameter grafts (P = 0.002). Graft thrombosis developed in the first month in 22 of 61 (36%) patients receiving fluoropolymer coated grafts compared to six of 68 (8.8%) patients receiving PTFE, which accounts for the difference in primary patency. Successful thrombectomy in 10 of the 22 fluoropolymer coated grafts resulted in similar secondary patency. CONCLUSION: Polytetrafluoroethylene has superior primary patency and similar secondary patency to fluoropolymer coated Dacron. These results support the preferential use of PTFE in patients with critical limb ischaemia, especially when a below-knee distal anastomosis and smaller diameter graft is required.

Triple compartment prolapse: sacrocolpopexy with anterior and posterior mesh extensions.

Post-hysterectomy vault prolapse may be accompanied by anterior (cystocele) and posterior (rectocele) pelvic compartment prolapse. We describe our results with sacrocolpopexy with anterior and posterior polytetrafluoroethylene mesh (SCAPM) extensions. A prospective on-going study is presented of 12 consecutive, complicated patients referred to our tertiary referral unit with a median age of 60 years (range 39-69) who underwent SCAPM between April 1997 and June 1999. All patients had a history and physical examination, International Continence Society Prolapse Staging (ICS) and pre-operative multichannel urodynamics testing with their prolapse reduced. All patients had an ICS grade 2, triple compartment prolapse or worse for inclusion into this study. The operative results were assessed with a 10-point visual analogue scale (VAS) for personal satisfaction and the (non-validated) St George's Hospital symptom questionnaire assessing urgency, urge incontinence, stress incontinence, splinting, digitation, sexual activity and function. All patients were reviewed during February 2002 by an independent observer (B.G. gynaecologist) no longer associated with the Department of Urogynaecology. All patients were followed post-operatively for a median of 39 months (range 32-58). One patient had a recurrent grade 1 cystocele and another a grade 1 rectocele. The median VAS score for personal satisfaction with the operative results was 8 (range 6-10). There was one patient with de novo urgency and one with de novo stress incontinence. Four of the five patients who needed to splint or digitate to empty the rectum no longer required these measures post-operatively. There were no reports of de novo dyspareunia, and two patients had improved vaginal lubrication. Two patients, each with more than five prior vaginal procedures, had a total of three episodes of mesh erosion through the posterior vaginal wall. The SCAPM is an effective treatment for triple compartment prolapse and incomplete rectal emptying. Patient satisfaction is good.

Epigard: a synthetic skin substitute with application to podiatric wound management.

The authors present a synthetic skin substitute, Epigard, which was developed in 1973 and has been used worldwide for temporary coverage of open wounds. Epigard is a two-layer, non-medicated wound dressing which approximates the function of human skin. The article discusses the proper indications and usage of Epigard, as well as post operative wound management and definitive wound closure decisions. A case presentation involving a serious diabetic wound infection is discussed. At Doctors Hospital, Epigard has become an important adjunctive therapy in wound management by improving wound healing time and decreasing patient hospital stay.

Avaliaçäo das alteraçöes oculares pelo uso prolongado de lentes de contato fluorcarbonadas / Valuation of ocular changes induced by extended wear fluoro-silicone/acrylate contact lenses

As alteraçöes oculares pelo uso prolongado das LC FLUORCARBONADAS (POLYSIL - FC) foram estudadas em 19 pacientes míopes de -1,00 a -4,25 D, com idade média de 23,9 anos, durante 12 semanas. Foram analisados os comportamentos da acuidade visual, do exame biomicroscópico do segmento anterior, da espessura corneana, da ceratometria, da estesiometria corneana, da topografia corneana pela fotoceratoscopia, da funçäo lacrimal pelo teste de Schirmer, e da pressäo intra-ocular pela tonometria de aplanaçäo. A espessura corneana apresentou aumento significativo apenas durante as duas primeiras semanas de uso das lentes de contato. A ceratometria evidenciou aplanamento corneano discreto, porém significativo, do meridiano vertical. Em relaçäo à acuidade visual, biomicroscopia do segmento anterior, estesiometria corneana, fotoceratoscopia, tonometria de aplanaçäo e teste de Schirmer, näo houve diferença significativa entre os valores obtidos antes e após a adaptaçäo das lentes de contato. Os resultados foram semelhantes em ambos os olhos. O uso prolongado destas lentes mostrou ser bastante seguro, näo ocorrendo nenhum caso de infecçäo ocular, alteraçäo da acuidade visual ou edema corneano significativo após o período estudado.

[Treatment of decubitus ulcer using a synthetic skin substitute]. / Methodik der Therapie von Dekubitalulzera mit synthetischem Hautersatzmaterial.

Due to the loss of topesthesia and to the impairment of the vasomotorium in the paralyzed area, patients suffering from tetraplegia have a high risk from pressure sores. Bed sores respond successfully to therapy if, on observing the relevant basic nursing procedure--requiring in particular that the damaged areas of skin be consistently relieved from pressure by means of special positioning of the patient--the sores are subjected to intensive cleansing via surgical and/or enzymatic débridement, and are conditioned with the synthetic skin substitute Epigard. This is achieved as a result of therapeutic procedure followed in a series of methodical steps. Specific treatment with antibiotics before conditioning the wounds supplements these measures and facilitates the spontaneous healing of the lesions or, in the case of larger bed sores, the optimal preparation of the wound bed prior to skin grafting and plastic surgery.

[Therapy of toxin absorption in skin burns. Synthetic skin replacement or tannic acid (author's transl)]. / Zur therapeutischen Beeinflussbarkeit der Toxinresorption bei Hautverbrennungen. Synthetischer Hautersatz oder Tanningerbung.

The influence of toxic factors from burned skin on pathogenesis of burn disease has been demonstrated in recent years. For preparation for skin transplantation synthetic material is used. The present study was undertaken to investigate if such material could inhibit the resorption of toxic factors. Specific mitochondrial alterations, which are reproducibly found 5 days after skin burn or application of burn toxin, served as parameter. Rats, which were treated shortly after burn or later with tannic acid were used as controls. Glucose and urea were measured in serum to check the synthetic function. Therapy with Epigard resulted in a better general condition and normal values of glucose and urea, but no reduction of specific mitochondrial alterations. Treatment with tannic acid caused no improvement in general condition, glucose and urea levels were not significantly altered. Only the early application resulted in a reduction of mitochondrial alterations. An otherwise indicated therapy with a synthetic skin material is not suitable for inhibition of the resorption of toxic factors from burnt skin.

Prophylaxis of predisposed otitis externa.

Evaluation, in the guinea pig ear, of fourteen water repellent or therapeutic compounds has resulted in the recommended use of 360 Medical Fluid as a prophylactic agent for those persons with a high risk of otitis externa. This compound was found to adhere well, be easy to apply and was nonirritating. Use of this material prevented adverse bacterial growth in ear canals exposed to water for up to seven days. The significance of maintaining the normal Gram positive bacterial flora in the external ear canal and the role of cerumen in maintaining a healthy meatal surface is discussed. A system for monitoring the health of the ear canal through measurement of the Gram positive/Gram negative bacterial ratio is suggested.