Incidence and Risk Model of Post-Traumatic Hydrocephalus in Patients with Traumatic Brain Injury.

OBJECTIVE: Post-traumatic hydrocephalus (PTH) is a complication following traumatic brain injury (TBI). Early diagnosis and treatment are essential to improving outcomes. We report the incidence and risk factors of PTH in a large TBI population while considering death as a competing risk. METHODS: We conducted a retrospective cohort study on consecutive TBI patients with radiographic intracranial abnormalities admitted to our academic medical center from 2009 to 2015. We assessed patient demographics, perioperative data, and in-hospital data as risk factors for PTH using survival analysis with death as a competing risk. RESULTS: Among 7,473 patients, the overall incidence of PTH requiring shunt surgery was 0.94%. The adjusted cumulative incidence was 0.99%. The all-cause cumulative hazard for death was 32.6%, which was considered a competing risk during analysis. Craniectomy (HR 11.53, P < 0.001, 95% CI 5.57-223.85), venous sinus injury (HR 4.13, P = 0.01, 95% CI 1.53-11.16), and age ≤5 (P < 0.001) were significant risk factors for PTH. Glasgow Coma Score (GCS) > 13 was protective against shunt placement (HR 0.50, P = 0.04, 95% CI 0.26-0.97). Shunt surgery occurred after hospital discharge in 60% of patients. CONCLUSIONS: We describe the incidence and risk factors for PTH in a large traumatic brain injury (TBI) population. Most cases of PTH were diagnosed after hospital discharge, suggesting that close follow-up and multidisciplinary diagnostic vigilance for PTH are needed to prevent morbidity and disability.

Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

Cross-linked chitosan biofunctionalized paper-based microfluidic device towards long term stabilization of blood typing antibodies.

Long term stability of antibodies at room temperature is a major challenge in the commercialization of point-of-care devices for diagnostics. Since chitosan has been proven to be an excellent biofunctionalization material, the effects of four different biofunctionalization processes were studied to improve the room temperature stability of antibodies immobilized on chitosan modified paper-based microfluidic devices using blood typing antibodies as candidates. The devices used in this work have a flower-shaped design with 4 test zones at each corner. In three zones Anti-A, Anti-B, and Anti-D (Anti-Rh) antibodies are immobilized and the fouth zone represents the control (no antibodies) after biofunctionalization. The biofunctionalization of the paper devices was done with chitosan and chitosan cross-linked with sodium triphosphate pentabasic, glutaraldehyde, and sodium hydroxide. These devices were used for blood typing assays using real blood samples. A similar assay was also performed on unmodified (non-biofunctionalized) paper devices for comparison. Chitosan based biofunctionalized paper-devices showed better stability, up to 100 days as compared to 14 days on unmodified paper, at room temperature. Such biofunctionalized paper-based devices will be suitable for on-field and remote testing without any technical expertise and requirement for the cold chain.

Surface-Engineered Paper Hanging Drop Chip for 3D Spheroid Culture and Analysis.

Protein corona coated onto the hydrophilic cellulose fiber turns into hydrophobic upon UV irradiation without hindering the porosity of the paper while simultaneously reducing nonspecific adsorption. Taking advantage of the biofouling-resistant, hydrophobic, and fluid transport through property, we demonstrated hanging drop three-dimensional (3D) spheroid culture and in-site analysis, including drug testing, time-dependent detection of secreted protein, and fluorescence staining without disturbing the spheroids. This single hanging drop system can also be extended to a networked hanging drop chip to mimic in vivo microphysiology by combining with wax-patterned microfluidic channels, where well-to-well interaction can be accurately controlled in a passive manner. As a proof of concept, the effects of a concentration gradient of nutrient and variable dosage of anticancer drugs were studied in the 3D spheroids cultured on paper. The experimental results suggested that a complex network device could be fabricated on a large scale on demand at a minimal cost for 3D spheroid culture. Our method demonstrates a future possibility for paper as a low cost, high-throughput 3D spheroid-based "body-on-a-chip" platform material.

Cloaked Exosomes: Biocompatible, Durable, and Degradable Encapsulation.

Exosomes-nanosized extracellular vesicles (EVs) naturally secreted from cells-have emerged as promising biomarkers and potential therapeutic vehicles, but methods to manipulate them for engineering purposes remain elusive. Among the technical obstacles are the small size and surface complexity of exosomes and the complex processing steps required, which reduce the biocompatibility of currently available methods. The encapsulation of exosomes with a nanofilm of supramolecular complexes of ferric ions (Fe3+ ) and tannic acid is demonstrated here. The resulting natural polyphenol, ≈10 nm thick, protects exosomes from external aggressors such as UV-C irradiation or heat and is controllably degraded on demand. Furthermore, gold nanoparticles can be covalently attached for single-exosome level visualization. To fully exploit their therapeutic potential, chemotherapeutic drug-loaded EVs are functionalized to achieve the targeted, selective killing of cancer cells preferentially over normal cells. This nanofilm not only preserves the native size and chemical makeup of the intrinsic exosomes, but also confers new capabilities for efficient tumor targeting and pH-controlled release of drugs. Demonstrating a scalable method to produce biocompatible, durable, on-demand degradable, and chemically controllable shields for exosome modification and functionalization, the methods introduced here are expected to bring the potential of exosome-based nanomedicine applications closer to reality.

Challenges and Opportunities of Centrifugal Microfluidics for Extreme Point-of-Care Testing.

The advantages offered by centrifugal microfluidic systems have encouraged its rapid adaptation in the fields of in vitro diagnostics, clinical chemistry, immunoassays, and nucleic acid tests. Centrifugal microfluidic devices are currently used in both clinical and point-of-care settings. Recent studies have shown that this new diagnostic platform could be potentially used in extreme point-of-care settings like remote villages in the Indian subcontinent and in Africa. Several technological inventions have decentralized diagnostics in developing countries; however, very few microfluidic technologies have been successful in meeting the demand. By identifying the finest difference between the point-of-care testing and extreme point-of-care infrastructure, this review captures the evolving diagnostic needs of developing countries paired with infrastructural challenges with technological hurdles to healthcare delivery in extreme point-of-care settings. In particular, the requirements for making centrifugal diagnostic devices viable in developing countries are discussed based on a detailed analysis of the demands in different clinical settings including the distinctive needs of extreme point-of-care settings.

Foil assisted replica molding for fabrication of microfluidic devices and their application in vitro.

We present a simple, rapid, benchtop, Foil Assisted Rapid Molding (FARM) method for the fabrication of microfluidic devices. This novel technique involves the use of aluminium foil, pen and an X-Y plotter to create semi-circular or plano-concave, shallow microchannels. It is an easy do-it-yourself (DIY) technique for creating a microfluidic device in three simple steps: (1) create a channel design using the CAD software, (2) plot the patterns on aluminium foil and (3) use the reverse of the engraved foil as a mold to create microfluidic devices. In this report, we present a detailed study of the proposed method by varying a range of parameters such as foil thickness, tip material, and tip sizes and by investigating their effect on the creation of channels with varying geometry. Furthermore, we demonstrated the cytocompatibility of these devices in vitro.

A double blind study on the efficacy of local application of hemocoagulase solution in wound healing.

AIM: The present double blind study has been designed to evaluate the efficacy of local application of hemocoagulase solution as compared to a placebo in wound healing following dental extraction. MATERIALS AND METHODS: A total of 20 patients who required dental extraction for orthodontic intervention were included. The hemocoagulase solution and a placebo were locally applied to the extraction sockets and the efficacy of the solution in terms of bleeding control, anti-inflammatory responses, its antiseptic properties and efficacy in wound healing were evaluated. RESULTS: The mean time required to achieve hemostasis was found to be 1.37 minutes in side A (test) and 2.33 minutes in side B (control) indicating that side A achieved faster hemostasis when compared to side B. At the 6th hour postoperatively, bleeding was not evident on either sides, and the amount of pain in side A was found to be less compared to side B. The number of RBCs, polymorphs, chronic inflammatory cells were not different in both the groups, whereas at 3rd postoperative day epithelial cells were greater in side A (test) compared to side B (control). Biopsy reports on the 12th postoperative day indicated that the number of fibroblasts, epithelial cells, collagen count was found to be greater in side A (test) compared to side B (control). CONCLUSION: The topical hemocoagulase solution may be advocated in the field of oral and maxillofacial surgery, as a hemostatic agent and promoter of wound healing. However, further studies, with large number of cases and different clinical situations should be considered to authenticate the efficacy of this hemocoagulase solution in the practice of oral and maxillofacial surgery. CLINICAL SIGNIFICANCE: Wound healing plays an important role in the success of any surgical procedure, such as extractions, and the hemocoagulase system may act as a hemostatic agent and a promoter of wound healing.

Risk factors for litigation following major transectional bile duct injury sustained at laparoscopic cholecystectomy.

BACKGROUND: Bile duct injuries after laparoscopic cholecystectomy often cause long-term morbidity, with a number of patients resorting to litigation. The present study aimed to analyze risk factors for litigation and to quantify the subsequent medicolegal burden. METHODS: A total of 67/106 patients (26 male) with major laparoscopic cholecystectomy bile duct injuries (LCBDI) and a minimum 2-year follow-up, replied to a questionnaire covering patient perception toward the complication, physical/psychological recovery, and subsequent litigation. These data were collated with prospectively collected data related to the LCBDI and subsequent management, and a multivariate regression model was designed to identify potential risk factors associated with litigation. RESULTS: Most patients felt they had been inadequately informed prior to surgery [47/67 (70%)] and after the LCBDI [50/67 (75%)], and a majority remained psychologically traumatized at the time of evaluation [50/67 (75%)]. Of these, 22 patients had started litigation by means of a "letter of demand" (LOD; n = 10) or prosecution (n = 12). Nineteen (19/22%) cases have been closed in favor of the plaintiff. There was no difference between the awards for LOD versus prosecution cases, and average compensation was £40,800 versus £89,875, respectively (p = n.s). On multivariate analysis, age < 52 years (p = 0.03), associated vascular injury (p = 0.014), immediate nonspecialist repair (p = 0.009), and perceived incomplete recovery following LCBDI (p = 0.017) were identified as independent predictors for possible litigation. CONCLUSIONS: On the basis of the present study, nearly one third of patients with major transectional LCBDI are likely to resort to litigation. Younger patients and those in whom repair is attempted prior to specialist referral are likely to initiate litigation.

Breast carcinoma metastatic to the bladder and renal pelvis requiring fulguration.

Breast cancer metastatic to the bladder has rarely been reported in the literature. A patient presented to our institution with pathologically confirmed breast cancer metastatic to the bladder with renal pelvis involvement as seen on retrograde pyelography. We believe cystoscopy with biopsy and fulguration to be the treatment of choice for breast cancer that has metastasized to the bladder because of the low rate of survival in patients with hematuria related to metastatic breast cancer.

Using intense pulsed light for cosmetic purposes: our experience.

The authors' experience using intense pulsed light for skin rejuvenation is summarized and analyzed with regard to its efficacy, safety, and complications. Rejuvenation using intense pulsed light was performed on 59 patients over a 6-month period (January of 2002 to July of 2002); these patients served as the study group. The areas treated were the face, neck, chest, hands, and legs. The parameters used during the procedure, patient satisfaction, and complications are described. Ninety-five percent of the patients included in the study had one or two sessions. Good to very good results were reported by 93.1 percent. Most patients had minor side effects and only three patients (5 percent) experienced complications (hyperpigmentation or scars). Intense pulsed light is an effective and safe method for skin rejuvenation. Its efficacy is mainly manifested by eliminating senile pigmentation and telangiectasias and a achieving a younger and fresher appearance of the skin. Although in the literature intense pulsed light skin rejuvenation is mainly reported for the face, the authors have obtained good results by using it for other areas of the body. The majority of the patients were satisfied. The authors conclude that intense pulsed light skin rejuvenation is a safe and effective method for facial and nonfacial rejuvenation.