Search

Background Home blood pressure measurements have equal or even greater predictive value than clinic blood pressure measurements regarding cardiovascular outcomes. With advances in home blood pressure monitors, we face an imminent flood of home measurements, but current electronic health record systems lack the functionality to allow us to use this data to its fullest. We designed a data visualization display for blood pressure measurements to be used for shared decision making around hypertension. Methods We used an iterative, rapid-prototyping, user-centred design approach to determine the most appropriate designs for this data display. We relied on visual cognition and human factors principles when designing our display. Feedback was provided by expert members of our multidisciplinary research team and through a series of end-user focus groups, comprised of either hypertensive patients or their healthcare providers required from eight academic, community-based practices in the Midwest of the United States. Results A total of 40 participants were recruited to participate in patient (N = 16) and provider (N = 24) focus groups. We describe the conceptualization and development of data display for shared decision making around hypertension. We designed and received feedback from both patients and healthcare providers on a number of design elements that were reported to be helpful in understanding blood pressure measurements. Conclusions We developed a data display for substantial amounts of blood pressure measurements that is both simple to understand for patients, but powerful enough to inform clinical decision making. The display used a line graph format for ease of understanding, a LOWESS function for smoothing data to reduce the weight users placed on outlier measurements, colored goal range bands to allow users to quickly determine if measurements were in range, a medication timeline to help link recorded blood pressure measurements with the medications a patient was taking. A data display such as this, specifically designed to encourage shared decision making between hypertensive patients and their healthcare providers, could help us overcome the clinical inertia that often results in a lack of treatment intensification, leading to better care for the 35 million Americans with uncontrolled hypertension.

Current human papilloma virus (HPV) vaccines provide substantial protection against the most common HPV types responsible for oral and anogenital cancers, but many circulating cancer-causing types remain that lack vaccine coverage. The novel RG1-VLP (virus-like particle) vaccine candidate utilizes the HPV16-L1 subunit as a backbone to display an inserted HPV16-L2 17–36 a.a. “RG1” epitope; the L2 RG1 epitope is conserved across many HPV types and the generation of cross-neutralizing antibodies (Abs) against which has been demonstrated. In an effort to heighten the immunogenicity of the RG1-VLP vaccine, we compared in BALB/c mice adjuvant formulations consisting of novel bacterial enzymatic combinatorial chemistry (BECC)-derived toll-like receptor 4 (TLR4) agonists and the aluminum hydroxide adjuvant Alhydrogel. In the presence of BECC molecules, consistent improvements in the magnitude of Ab responses to both HPV16-L1 and the L2 RG1 epitope were observed compared to Alhydrogel alone. Furthermore, neutralizing titers to HPV16 as well as cross-neutralization of pseudovirion (PsV) types HPV18 and HPV39 were augmented in the presence of BECC agonists as well. Levels of L1 and L2-specific Abs were achieved after two vaccinations with BECC/Alhydrogel adjuvant that were equivalent to or greater than levels achieved with 3 vaccinations with Alhydrogel alone, indicating that the presence of BECC molecules resulted in accelerated immune responses that could allow for a decreased dose schedule for VLP-based HPV vaccines. In addition, dose-sparing studies indicated that adjuvantation with BECC/Alhydrogel allowed for a 75% reduction in antigen dose while still retaining equivalent magnitudes of responses to the full VLP dose with Alhydrogel. These data suggest that adjuvant optimization of HPV VLP-based vaccines can lead to rapid immunity requiring fewer boosts, dose-sparing of VLPs expensive to produce, and the establishment of a longer-lasting humoral immunity.

Shigella ssp cause bacillary dysentery (shigellosis) which has high global morbidity in young children and the elderly. The virulence of Shigella relies upon a type III secretion system (T3SS) which injects host altering effector proteins into targeted intestinal cells. The Shigella T3SS contains two components, invasion plasmid antigen D (IpaD) and invasion plasmid antigen B (IpaB), that were previously identified as broadly protective antigens. When IpaD and IpaB were co-expressed to give the DB fusion (DBF) protein, vaccine efficacy was further improved. Biophysical characterization under various pH conditions showed that DBF is most stable at pH 7 and 8 and loses its conformational integrity at 48 and 50 °C respectively. Forced degradation studies revealed significant effects on the secondary structure, tertiary structure and conformational stability of DBF. In the presence of phosphate buffers as well as other anionic excipients, DBF demonstrated a concentration dependent conformational stabilization. Molecular docking revealed potential polyanion binding sites in DBF that may interact with phytic acid. These sites can be exploited to stabilize the DBF protein. This work highlights potential destabilizing and stabilizing factors, which not only improves our understanding of the DBF protein but helps in future development of a stable Shigella vaccine.

Introduction Injectable semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that was previously shown to be superior to liraglutide and dulaglutide in head-to-head comparisons in GLP-1 RA-naïve individuals. It is hypothesized that semaglutide will cause further reductions in glycated hemoglobin A1c (HbA1c) and weight in type 2 diabetes mellitus (T2DM) patients previously treated with liraglutide or dulaglutide. The REALISE-DM study provides the first real-world evidence of the effectiveness and tolerability of semaglutide in patients switching from another GLP-1 RA. Methods This retrospective real-world effectiveness analysis included T2DM adults who were on a stable dose of liraglutide or dulaglutide prior to switching to semaglutide. The primary outcome was change in HbA1c. Secondary outcomes were the changes in weight and body mass index (BMI), the occurrence of gastrointestinal side effects (GSEs), and discontinuations. Linear mixed models were used to estimate changes in HbA1c, weight, and BMI, and logistic regression was employed to analyze GSEs and discontinuations. Results Six months after the 164 patients in this study had switched to semaglutide, their mean HbA1c had decreased by 0.65% (7.1 mmol/mol) (95% prediction interval [PI]: 0.48, 0.81% [5.2, 8.9 mmol/mol]) from a baseline of 7.9% (interquartile range [IQR]: 7.3, 8.8) (62.8 mmol/mol [IQR: 56.3, 72.7]), while their weight and BMI had reduced by 1.69 kg (95% PI: 1.01, 2.37) and 0.59 kg/m2 (95% PI: 0.34, 0.84), respectively. Nineteen patients (11.6%) developed GSEs after switching. Conclusions This study supports switching T2DM patients on liraglutide or dulaglutide to injectable semaglutide to achieve further reductions in HbA1c and weight. Although a small number of GSEs occurred, semaglutide was well tolerated by the majority of the patients. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-020-00984-x.

The serotype-specific early detection of dengue fever is very effective in predicting the pervasiveness of fatal infections such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). This fever results from reinfection (secondary) with a serotype of the dengue virus, which is different from the serotype involved in primary infection. Hence, the present work was aimed to develop a multiplexed electrochemical paper-based analytical device (ePAD) consisting of graphene oxide-silicon dioxide (GO-SiO

Cabazitaxel, a novel tubulin inhibitor with poor affinity for P-glycoprotein, is a second-generation taxane holding great promise for the treatment of metastatic castration-resistant prostate cancer. However, its poor solubility and lack of target-ability limit its therapeutic applications. Herein, we develop a biodegradable, enzyme-responsive, and targeted polymeric micelle for cabazitaxel. The micelle is formed from two amphiphilic block copolymers. The first block copolymer consists of PEG, an enzyme-responsive peptide, and cholesterol; whereas the second block copolymer consists of a targeting ligand, PEG and cholesterol. The enzyme-responsive peptide is cleavable in the presence of matrixmetaloproteinase-2 (MMP-2), which is overexpressed in the tumor microenvironment of prostate cancer. The micelle showed a very low critical micelle concentration (CMC), high drug loading, and high entrapment efficiency. Release of cabazitaxel from the micelle is dependent on the cleavage of the enzyme-responsive peptide. Moreover, the micelle showed dramatically higher cellular uptake in prostate cancer cells compared to free cabazitaxel. Importantly, the ligand-coupled polymeric micelle demonstrated better inhibition of tumor growth in mice bearing prostate cancer xenografts compared to unmodified micelle and free cabazitaxel. Taken together, these findings suggest that the enzyme-responsive cabazitaxel micelle is a potent and promising drug delivery system for advanced prostate cancer therapy. STATEMENT OF SIGNIFICANCE: Herein, we develop a biodegradable, enzyme-responsive, and actively targeted polymer micelle for cabazitaxel, which is a novel tubulin inhibitor with poor affinity for P-glycoprotein. Despite cabazitaxel's great promise for metastatic castration-resistant prostate cancer, its poor solubility, lack of target-ability, and high systemic toxicity limit its therapeutic applications, and therefore a targeted delivery system is highly needed for cabazitaxel. Our results demonstrate the importance of active targeting in targeted prostate cancer therapy. Encapsulating cabazitaxel in the micelle increases its activity and is expected to reduce its systemic toxicity, which is a major hurdle in its clinical applications. Moreover, the polymeric micelle may servers as a promising nanoscale platform for the targeted delivery of other chemotherapeutic agents to prostate cancer.

The basic purpose of a vaccine is to simulate certain structural features of a pathogen or other target entities. Initially, successful vaccines consisted of live, attenuated, or inactivated organisms. It was later found that components of such organisms could be used as vaccines, although additional immunological stimulation by adjuvants is often required. The successful use of crude preparations of toxins such as those of diphtheria, tetanus, and pertussis was especially encouraging. The advent of recombinant DNA technology raised the hope that it would now be possible to create safe vaccines for virtually any disease by synthesizing chemically well-defined proteins such as those on the surface of viruses and bacteria that could induce a strong, neutralizing immune response. Since therapeutic proteins have a well-established history of formulation development and use in humans, it was assumed that their transformation to vaccines would be relatively straightforward. This has turned out not be the case, however. While initial success with vaccines for hepatitis B and human papilloma virus was striking, their virus-like particle nature (self-assembled virus surface proteins) proved to be a major reason for their success. This no doubt reflects their highly similar nature to the actual target pathogen. Very recent success with a recombinant protein-based vaccine for serogroup B-induced meningitis and shingles again suggests the potential utility of such vaccines. We are still left, however, with the quandary of the failure of the vast majority of recombinant vaccines to provide protective immune responses. In this chapter, we will consider the challenges associated with the development and use of recombinant protein-based vaccines and then provide five examples of such vaccines undergoing clinical evaluation. We will then discuss challenges for future protein-based vaccine development.

Conjoined twins represent a very rare congenital anomaly, and the dicephalic dibrachius dipus (DDD) type of conjoined twinning is so rare that the exact prevalence is unknown. Only a few published case studies have mentioned this anomaly. Not enough data are available where antenatal ultrasonography (USG) and MRI have been employed in the workup of such cases. This study describes the case of a 24-year-old woman who came to our department for an anomaly scan at 25 weeks of gestation and was diagnosed with a dicephalic type of conjoined twinning with multiple anomalies. However, USG could not differentiate between DDD twinning and craniopagus parasiticus; hence, the patient was referred for fetal MRI. On MRI, the diagnosis of DDD was confirmed. In craniopagus parasiticus twinning, the surgical removal of the parasitic head can allow an everyday life. However, DDD twinning with multiple anomalies is not compatible with life, and the mother was thoroughly explained the grave prognosis. In such doubtful cases, fetal MRI should always be employed to ascertain the diagnosis for proper management and counseling.

Desmoplasia plays a pivotal role in promoting pancreatic cancer progression and is associated with poor clinical outcome. Targeting the desmoplastic tumor microenvironment in combination with chemotherapy is therefore a promising strategy for pancreatic cancer therapy. Here, we report a novel biodegradable copolymer to codeliver LY2109761 (a TGF-β receptor I/II inhibitor) and CPI-613 (a novel chemotherapy agent) to desmoplastic stroma and tumor cells, respectively, in the tumor microenvironment. Hydrophobic CPI-613 is conjugated to the hydrophilic copolymer via a newly designed MMP-2-responsive linker to form a trigger-responsive nanopolyplex. LY2109761 is hydrophobic and encapsulated into the hydrophobic core of the nanopolyplex. The resulting nanopolyplex is modified with a plectin-1-targeting peptide to enhance the accumulation of the nanopolyplex in pancreatic tumors. The nanopolyplex aims to normalize the stroma by blocking the interaction between tumor cells and pancreatic stellate cells to inhibit the activation of pancreatic stellate cells and subsequently reduce the dense extracellular matrix. Normalized stroma increases the penetration of the nanopolyplex into the tumor. The nanopolyplex shows enhanced accumulation in xenograft pancreatic tumors in a biodistribution study. Moreover, the targeted nanopolyplex markedly inhibits tumor growth in an orthotopic pancreatic cancer mouse model by dual-targeting tumor cells and stroma. Overall, the multifunctional nanopolyplex is a promising platform for pancreatic cancer therapy.

This report presents a novel lab-on-a-paper (LoP)-based device coupled with a molybdenum disulfide nanosheet (MoS2NS)-modified electrochemical genosensor for detecting Salmonella-specific DNA. Conductive electrodes were grafted on a paper-based substrate employing a stencil printing technique, and MoS2NS was decorated on the working electrode. MoS2NS has strong affinity toward nucleo bases, which made it a best sensing interface for the immobilization of DNA. Morphological, optical, and structural characterizations were accomplished using X-ray diffraction (XRD), high-resolution transmission electron microscopy (HR-TEM), UV–vis spectroscopy (UV–vis), and Raman spectroscopy, repectively. The current studies of an electrochemical genosensor demonstrated a good linear detection range from 100–20 nM and a low limit of detection of 20 nM toward Salmonella DNA with R2 = 0.991. The proposed LoP-based genosensor confirmed as a better sensing podium and an effectual immobilization matrix for DNA.

Liver fibrosis is caused by excessive accumulation of extracellular matrix during chronic liver injuries. Although clinical evidence suggests that liver fibrosis can be reversed, there is no standard therapy for liver fibrosis. Moreover, there is a lack of diagnostic tools to detect early-stage liver fibrosis. Activation of hepatic stellate cells (HSCs) is the key step during liver fibrogenesis, and its mechanism has been extensively studied by various cell culture and animal models. Targeted delivery of therapeutic agents to activated HSCs is therefore critical for the successful treatment of liver fibrosis. A number of protein markers have been found to be overexpressed in activated HSCs, and their ligands have been used to specifically deliver various antifibrotic agents. In this review, we summarize these HSC-specific protein markers and their ligands for targeted delivery of antifibrotic agents.

Purpose: The purpose of this article is to investigate automated segmentation measurements of the outer nuclear layer to differentiate patients with hydroxychloroquine toxicity from healthy individuals. Methods: A 5-year retrospective, case-controlled, interventional study of hydroxychloroquine toxicity patients was conducted. Measurements of the outer nuclear layer were obtained with use of commercially available segmentation software and compared with controls. Results: Seven participants (13 eyes) with toxicity and 16 controls (16 eyes) were included. The data comparing the parafoveal, perifoveal, foveal, and overall regions were significant both in thickness ( P < .0001, P < .0001, P = .0029, and P < .0001, respectively) and volume ( P < .0001, P < .0001, P < .0001, and P < .0001, respectively). The CI indicates there is 95% confidence that toxicity patients have between 147 μm and 201 μm less thickness (average 174 μm) and between 0.39 mm3 and 0.55 mm3 less volume (average 0.47 mm3). Conclusions: The automated segmentation function can correctly differentiate thinner outer nuclear layer measurements in patients with toxicity. This study is the first to establish the ranges of thickness and volume of the outer nuclear layer with commercially available segmentation. These results provide the first step in determining whether automated segmentation measurements of the outer nuclear layer can be used as an objective screening tool for hydroxychloroquine toxicity.

Hyaluronic acid (HA)-based prodrugs bearing double-responsive (acid pH or oxidation) boronates of catechol-containing drugs were used to treat xenografted human prostate tumours (LNCaP) in SCID mice. The HA prodrugs accumulated significantly only in tumours (impressively, up to 40% of the injected dose after 24 h) and in liver, with negligible – actually anti-inflammatory - consequences in the latter. A quercetin-HA prodrug significantly slowed down tumour growth, in a dose-dependent fashion and with a much higher efficacy (up to 4 times) than equivalent doses of free quercetin. In short, boronated HA appears to be a very promising platform for targeted chemotherapy.

Liver fibrosis is a wound healing process with excessive accumulation of extracellular matrix in the liver. We recently discovered a PCBP2 siRNA that reverses fibrogenesis in activated hepatic stellate cells (HSCs), which are the key players in liver fibrogenesis. However, targeted delivery of siRNAs to HSCs still remains a challenge. Herein, we developed a new strategy to fabricate a multicomponent nanocomplex using siRNA/PNA hybrid instead of chemically conjugated siRNA, thus increasing the scalability and feasibility of the siRNA nanocomplex for animal studies. We modified the nanocomplex with an insulin growth factor 2 receptor (IGF2R)-specific peptide, which specifically binds to activated HSCs. The siRNA nanocomplex shows a controllable size and high serum stability. The nanocomplex also demonstrates high cellular uptake in activated HSCs in vitro and in vivo. Anti-fibrotic activity of the siRNA nanocomplex was evaluated in rats with carbon tetrachloride-induced liver fibrosis. Treatment with the PCBP2 siRNA nanocomplex significantly inhibits the mRNA expressions of PCBP2 and type I collagen in fibrotic liver. Histology study revealed that the siRNA nanocomplex efficiently reduces the protein level of type I collagen and reverses liver fibrosis. Our data suggest that the nanocomplex efficiently delivers the siRNA to fibrotic liver and produces a potent anti-fibrotic effect.

Objective. Uncontrolled hypertension is driven by clinical uncertainty around blood pressure data. This research sought to determine whether decision support—in the form of enhanced data visualization—could improve judgments about hypertension control. Methods. Participants (Internet sample of patients with hypertension) in 3 studies ( N = 209) viewed graphs depicting blood pressure data for fictitious patients. For each graph, participants rated hypertension control, need for medication change, and perceived risk of heart attack and stroke. In study 3, participants also recalled the percentage of blood pressure measurements outside of the goal range. The graphs varied by systolic blood pressure mean and standard deviation, change in blood pressure values over time, and data visualization type. Results. In all 3 studies, data visualization type significantly affected judgments of hypertension control. In studies 1 and 2, perceived hypertension control was lower while perceived need for medication change and subjective perceptions of stroke and heart attack risk were higher for raw data displays compared with enhanced visualization that employed a smoothing function generated by the locally weighted smoothing algorithm. In general, perceptions of hypertension control were more closely aligned with clinical guidelines when data visualization included a smoothing function. However, conclusions were mixed when comparing tabular presentations of data to graphical presentations of data in study 3. Hypertension was perceived to be less well controlled when data were presented in a graph rather than a table, but recall was more accurate. Conclusion. Enhancing data visualization with the use of a smoothing function to minimize the variability present in raw blood pressure data significantly improved judgments about hypertension control. More research is needed to determine the contexts in which graphs are superior to data tables.

Co-delivery of IKBKE siRNA and cabazitaxel inhibits invasiveness and growth of triple-negative breast cancer., IKBKE is an oncogene in triple-negative breast cancer (TNBC), and we demonstrate that IKBKE small interfering RNA (siRNA) inhibits the proliferation, migration, and invasion of TNBC cells. Despite the recent success of siRNA therapeutics targeting to the liver, there still remains a great challenge to deliver siRNAs to solid tumors. Here, we report a hybrid nanocomplex to co-deliver the IKBKE siRNA and cabazitaxel to TNBC to achieve an optimal antitumor effect. The nanocomplex is modified with hyaluronic acid to target CD44 on TNBC cells. The nanocomplex shows higher cellular uptake and better tumor penetration of the encapsulated cargos. The nanocomplex also exhibits high tumor accumulation and antitumor activity in an orthotopic TNBC mouse model. Encapsulation of cabazitaxel in the nanocomplex enhances the activity of the IKBKE siRNA. The hybrid nanocomplex provides a novel and versatile platform for combination therapies using siRNAs and chemotherapy.

Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) are an established treatment for patients with type 2 diabetes (T2D). Differences between GLP‐1RAs in pharmacokinetics, dosing regimens and clinical effects, including cardiovascular (CV) outcomes, mean there may be benefits to switching from one to another. However, clinical guidance on switching is lacking and data from clinical trials are limited. This article provides a clinical perspective and consensus on the benefits of switching between GLP‐1RAs, the triggers for switching and how best to manage this in clinical practice. Once weekly (OW) semaglutide is used as an example to illustrate how the authors might switch to a different GLP‐1RA in clinical practice. Methods Literature was searched and perspectives from 10 healthcare professionals with experience in switching patients with T2D to OW semaglutide from another GLP‐1RA were collated. Results Medical triggers for switching to another GLP‐1RA included HbA1c targets not being met, a desire for additional weight loss, poor adherence, patients moving to increased CV risk status and adverse effects with the current GLP‐1RA. Non‐medical triggers for switching included patient preference, cost, formulary changes and insurance mandates. Once the decision to switch is made, an individualised approach is recommended, based on considerations that include reimbursement requirements, treatment duration with (and dose of) previous GLP‐1RA, the patient's experience initiating the prior GLP‐1RA, any concomitant treatment and clinical characteristics. When switching, it is important to emphasise that treatment burden will not increase and that if gastrointestinal adverse effects occur, they are typically transient. Any transient gastrointestinal adverse effects that may occur (or recur) when switching to another GLP‐1RA can be reduced by slow up‐titration and advising patients to reduce food portion sizes and fat intake. Conclusion Switching from one GLP‐1RA to another, such as OW semaglutide, can provide clinical benefits and may delay the need for treatment intensification.

Background Nearly half of US adults with diagnosed hypertension have uncontrolled blood pressure. Clinical inertia may contribute, including patient-physician uncertainty about how variability in blood pressures impacts overall control. Better information display may support clinician-patient hypertension decision making through reduced cognitive load and improved situational awareness. Methods A multidisciplinary team employed iterative user-centered design to create a blood pressure visualization EHR prototype that included patient-generated blood pressure data. An attitude and behavior survey and 10 focus groups with patients (N = 16) and physicians (N = 24) guided iterative design and confirmation phases. Thematic analysis of qualitative data yielded insights into patient and physician needs for hypertension management. Results Most patients indicated measuring home blood pressure, only half share data with physicians. When receiving home blood pressure data, 88% of physicians indicated entering gestalt averages as text into clinical notes. Qualitative findings suggest that including a data visualization that included home blood pressures brought this valued data into physician workflow and decision-making processes. Data visualization helps both patients and physicians to have a fuller understanding of the blood pressure ‘story’ and ultimately promotes the activated engaged patient and prepared proactive physician central to the Chronic Care Model. Both patients and physicians expressed concerns about workflow for entering and using home blood pressure data for clinical care. Conclusions Our user-centered design process with physicians and patients produced a well-received blood pressure visualization prototype that includes home blood pressures and addresses patient-physician information needs. Next steps include evaluating a recent EHR visualization implementation, designing annotation functions aligned with users’ needs, and addressing additional stakeholders’ needs (nurses, care managers, caregivers). This significant innovation has potential to improve quality of care for hypertension through better patient-physician understanding of control and goals. It also has the potential to enable remote monitoring of patient blood pressure, a newly reimbursed activity, and is a strong addition to telehealth efforts.

Purpose To quantify the torsional load to fracture for subpectoral biceps tenodesis with interference screw fixation. Methods We randomized 28 specimens from 14 matched-pair full-length humeri (mean age, 55.3 years) into 3 groups: (1) empty ream group (ERG), (2) screw-only group (SOG), and (3) screw–plus–biceps tendon group (SBG). In each group, 1 humerus of each matched pair was prepared according to group allocation and the contralateral humerus remained intact as a control. In the ERG, an 8-mm unicortical hole was reamed 1 cm proximal to the inferior border of the pectoralis major tendon insertion; in the SOG, the humerus was filled with an 8-mm × 12-mm PEEK (polyether ether ketone) screw; and in the SBG, the humerus was filled with a PEEK screw and the cadaveric long head of the biceps tendon. Humeri were tested under torsional displacement at a rate of 1°/s until fracture. Maximum torque, energy to maximum torque, and linear stiffness were used to assess humerus strength. Results Compared with contralateral intact specimens, the maximum torque to fracture was reduced by 28% in the ERG ( P = .005), 30% in the SOG ( P = .014), and 20% in the SBG ( P = .046). Energy to maximum torque was similarly reduced in the ERG ( P = .007), SOG ( P = .023), and SBG ( P = .049). Stiffness was increased by 4% in the ERG ( P = .498), 9% in the SOG ( P = .030), and 4% in the SBG ( P = .439). Conclusions Drilling an 8-mm unicortical hole in zone 3 of the bicipital tunnel for open subpectoral biceps tenodesis reduces the torsional load to humeral fracture up to 28% at time 0. The addition of a PEEK tenodesis screw alone reduced the maximum torque by 30%, and the addition of a screw with the long head of the biceps tendon reduced the maximum torque by 20%. The total load to fracture was reduced in all settings. Stiffness was not significantly different for the ERG and SBG, but stiffness was significantly higher for the SOG compared with the intact matched humeri at time 0. Clinical Relevance When performing a biceps tenodesis, humeral fracture susceptibility is increased with an applied torsional load at time 0. Thus providers must be aware of this reduced integrity when a subpectoral biceps tenodesis is used.

Insulin-like growth factor 2 receptor (IGF2R) is overexpressed in activated Hepatic stellate cells (HSCs) and therefore can be utilized for HSC-specific drug delivery. We recently discovered an IGF2R-specific peptide using a novel biopanning. Here, we adopted biotin-conjugated IGF2R-specific peptide, cholesterol, and vitamin A as the targeting ligands for the neutravidin-based siRNA nanocomplex to deliver PCBP2 siRNA, a potentially antifibrotic agent, to HSCs. Compared to Vitamin A and cholesterol, the IGF2R-specific peptide exhibited the highest targeting effect to human LX-2 HSC, rat HSC-T6 cell line, and activated primary rat HSCs. Accordingly, the IGF2R-specific peptide coupled nanocomplex demonstrated higher silencing activity of PCBP2 and better inhibition on the migration of activated HSCs. Compared to free siRNA and the nanocomplexes coupled with Vitamin A and cholesterol, the IGF2R-specific peptide coupled nanocomplex showed the highest uptake in the liver and lowest uptake in the lung and kidney of the rats with CCl4-induced liver fibrosis.

Purpose To compare the initial fixation stability, failure strength, and mode of failure of 5 different screw types and fixation methods commonly used for the classic Latarjet procedure. Methods Thirty-five fresh-frozen cadaveric shoulder specimens were allocated into 5 groups. A 25% anteroinferior glenoid defect was created, and a classic Latarjet coracoid transfer procedure was performed. All grafts were fixed with 2 screws, differing by screw type and/or fixation method. The groups included partially threaded solid 4.0-mm cancellous screws with bicortical fixation, partially threaded solid 4.0-mm cancellous screws with unicortical fixation, fully threaded solid 3.5-mm cortical screws with bicortical fixation, partially threaded cannulated 4.0-mm cancellous screws with bicortical fixation, and partially threaded cannulated 4.0-mm captured screws with bicortical fixation. All screws were stainless steel. Outcomes included cyclic creep and secant stiffness during cyclic loading, as well as load and work to failure during the failure test. Intergroup comparisons were made by a 1-way analysis of variance. Results There were no significant differences among different screw types or fixation methods in cyclic creep or secant stiffness after cyclic loading or in load to failure or work to failure during the failure test. Post-failure radiographs showed evidence of screw bending in only 1 specimen that underwent the Latarjet procedure with partially threaded solid cancellous screws with bicortical fixation. The mode of failure for all specimens analyzed was screw cutout. Conclusions In this biomechanical study, screw type and fixation method did not significantly influence biomechanical performance in a classic Latarjet procedure. When performing this procedure, surgeons may continue to select the screw type and method of fixation (unicortical or bicortical) based on preference; however, further studies are required to determine the optimal method of treatment. Clinical Relevance Surgeons may choose the screw type and fixation method based on preference when performing the Latarjet procedure.

We report the fabrication of high energy Li-ion capacitor (LIC) using teak wood sawdust derived mesoporous activated carbon (AC-HBP) with electrochemically pre-lithiated graphite (LiC6). Three interesting supercapacitor assemblies are constructed using AC-HBP to realize the high energy density. Amongst, AC-HBP paired with LiC6 delivered a maximum energy density of ∼111 Wh kg−1 compared to Li4Ti5O12 in LIC (∼53 Wh kg−1) and AC-HBP (∼37 Wh kg−1) in symmetric configurations. This excellent energy density is mainly ascribed to the tailored mesoporous nature (∼67%) of the high surface area activated carbon (2108 m2 g−1) obtained via hydrothermal carbonization process in the presence of processing agent, benzene tetracarboxylic acid followed by physico-chemical activation.

Avidin-biotin interaction is one of the strongest non-covalent interactions in the nature. Avidin and its analogues have therefore been extensively utilized as probes and affinity matrices for a wide variety of applications in biochemical assays, diagnosis, affinity purification, and drug delivery. Recently, there has been a growing interest in exploring this non-covalent interaction in nanoscale drug delivery systems for pharmaceutical agents, including small molecules, proteins, vaccines, monoclonal antibodies, and nucleic acids. Particularly, the ease of fabrication without losing the chemical and biological properties of the coupled moieties makes the avidin-biotin system a versatile platform for nanotechnology. In addition, avidin-based nanoparticles have been investigated as diagnostic systems for various tumors and surface antigens. In this review, we will highlight the various fabrication principles and biomedical applications of avidin-based nanoparticles in drug delivery and diagnosis. The structures and biochemical properties of avidin, biotin and their respective analogues will also be discussed.

Insulin like growth factor II receptor (IGFIIR) is a transmembrane protein overexpressed in activated hepatic stellate cells (HSCs), which are the major target for the treatment of liver fibrosis. In this study, we aim to discover an IGFIIR-specific aptamer that can be potentially used as a targeting ligand for the treatment and diagnosis of liver fibrosis. Systematic evolution of ligands by exponential enrichment (SELEX) was conducted on recombinant human IGFIIR to identify IGFIIR-specific aptamers. The binding affinity and specificity of the discovered aptamers to IGFIIR and hepatic stellate cells were studied using flow cytometry and Surface Plasmon Resonance (SPR). Aptamer-20 showed the highest affinity to recombinant human IGFIIR protein with a Kd of 35.5 nM, as determined by SPR. Aptamer-20 also has a high affinity (apparent Kd 45.12 nM) to LX-2 human hepatic stellate cells. Binding of aptamer-20 to hepatic stellate cells could be inhibited by knockdown of IGFIIR using siRNA, indicating a high specificity of the aptamer. The aptamer formed a chimera with an anti-fibrotic PCBP2 siRNA and delivered the siRNA to HSC-T6 cells to trigger silencing activity. In Vivo biodistribution study of the siRNA-aptamer chimera also demonstrated a high and specific uptake in the liver of the rats with CCl4-induced liver fibrosis. These data suggest that aptamer-20 is a high-affinity ligand for antifibrotic and diagnostic agents for liver fibrosis.

Background Immunotherapy using checkpoint inhibitors, especially PD-1/PD-L1 inhibitors, has now evolved into the most promising therapy for cancer patients. However, most of these inhibitors are monoclonal antibodies, and their large size may limit their tumor penetration, leading to suboptimal efficacy. As a result, there has been a growing interest in developing low-molecular-weight checkpoint inhibitors. Methods We developed a novel biopanning strategy to discover small peptide-based anti-PD-L1 inhibitors. The affinity and specificity of the peptides to PD-L1 were examined using various assays. Three-dimensional (3D) spheroid penetration study was performed to determine the tumor penetration capability of the peptides. Anti-tumor activity of the peptides was evaluated in mice bearing CT26 tumor cells. Results We discover several anti-PD-L1 peptide inhibitors to block PD-1/PD-L1 interaction. The peptides exhibit high affinity and specificity to human PD-L1 protein as well as PD-L1-overexpressing human cancer cells MDA-MB-231 and DU-145. Molecular docking studies indicate that the peptide CLP002 specifically binds to PD-L1 at the residues where PD-L1 interacts with PD-1. The peptide also blocks the CD80/PD-L1 interaction, which may further enhance the immune response of tumor-infiltrating T cells. Compared to antibody, the peptide CLP002 exhibits better tumor penetration in a 3D tumor spheroid model. The peptide CLP002 restores proliferation and prevents apoptosis of T cells that are co-cultured with cancer cells. The peptide CLP002 also inhibits tumor growth and increases survival of CT26 tumor-bearing mice. Conclusions This study demonstrated the feasibility of using phage display to discover small peptide-based checkpoint inhibitors. Our results also suggested that the anti-PD-L1 peptide represents a promising low-molecular-weight checkpoint inhibitor for cancer immunotherapy. Electronic supplementary material The online version of this article (10.1186/s40425-019-0705-y) contains supplementary material, which is available to authorized users.

Digital, Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p, Ciencias Médicas y de la Salud

Digital, Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6–8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1–5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79–0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80–1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p, Ciencias Médicas y de la Salud

An enzyme-responsive peptide drug conjugate was developed for TGX-D1, a promising PI3K inhibitor for prostate cancer therapy. LNCaP-specific KYL peptide was used as the targeting ligand and the prostate specific antigen (PSA) cleavable peptide (SSKYQSL) was used as the enzyme-responsive linker. SSKYQSL is cleaved by recombinant human PSA at 10–250 μg/mL. By contrast, the linker is stable in the serum of prostate cancer patients with high PSA levels (>500 ng/mL), indicating that this linker can survive the systemic circulation in prostate cancer patients but be cleaved in the tumor microenvironment. Cellular uptake of the peptide drug conjugate in prostate cancer cells is improved by about nine times. Biodistribution study reveals significant tumor accumulation of the peptide drug conjugate in nude mice bearing C4–2 tumor xenografts. Meanwhile, distribution of the conjugate in other major tissues is the same as the parent drug, indicating a high specificity of the conjugate to prostate cancers in vivo.

Background: Total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA) are effective treatments for glenohumeral arthritis and rotator cuff arthropathy. Purpose: To determine if the use of a post operative closed-suction drain following TSA and RTSA affects hemoglobin levels, clinical outcomes, and complications. Hypothesis: Patients who did not receive a drain will have less hemoglobin loss, better clinical outcome scores, and lower complication rates following TSA/RTSA. Methods: All patients who underwent TSA or RTSA by one of two surgeons between January 1, 2011 and May 15, 2013 were recorded. Patient demographic information was recorded. Patients were grouped based on use of a post-operative deep drain. Pre and post-operative hemoglobin, length of hospital stay, clinical outcome scores, and complications were recorded and analyzed. Results: Sixty-four patients (average age 58.9±9.9 years, 55% male) underwent RTSA (13) or TSA (51) without the use of a post-operative closed-suction drain; 304 patients (average age 66.7±9.6 years, 55% female) underwent RTSA (179) or TSA (125) with the use of a post-operative closed-suction drain. Average follow up was similar in both groups: 14.95±7.22 months in the drain group and 14.55±6.74 months in the no drain group (p=.723). Using multivariate analysis to control for confounding variables and differences between the two groups, drain usage was correlated with significantly lower postoperative hemoglobin (p=0.0002), longer length of stay (p≤0.0001), and lower postoperative SST (p=0.003). Conclusion: Closed-suction drain usage following RTSA and TSA leads to greater loss of hemoglobin and longer length of stay. No clinically significant differences in transfusion rate and clinical outcome scores were seen with or without drain usage. LEVEL OF EVIDENCE: III: case-control study.

Purpose To determine the trends in SLAP repairs over time, including patient age, and percentage of SLAP repairs versus other common shoulder arthroscopic procedures. Methods The records of 4 sports or shoulder/elbow fellowship trained orthopaedic surgeons were used to identify the total number of common shoulder arthroscopic cases performed between 2004 and 2014 using current procedural terminology codes (CPT): 29822, 29823, 29826, 29827, 29806, 29807, 29825, and 29828. The number of SLAP repairs (CPT code 29807) as a combined or isolated procedure were recorded, and the classification of SLAP type was undertaken using operative reports. Patient age was recorded. Linear regression was used to determine statistical significance. Results There were 9,765 patients who underwent arthroscopic shoulder procedures using the defined CPT codes between 2004 and 2014 by our 4 orthopaedic surgeons. Of these, 619 underwent a SLAP repair (6.3%); average age 31.2 ± 11.9. The age of patients undergoing SLAP repair significantly decreased over time ( P R 2 = 0.794). Most SLAP repairs were performed on type II SLAP tears ( P = .015, R 2 = 0.503). The percentage of SLAP repairs compared with the total number of shoulder arthroscopic surgeries and total number of patients who underwent SLAP repair significantly decreased over time ( P R 2 = 0.832 and P = .002, R 2 = 0.674, respectively). Conversely, the number and percentage of biceps tenodeses are increasing over time ( P = .0024 and P = .0099, respectively). Conclusions Over the past 10 years, the total number of biceps tenodeses has increased, whereas the number and relative percentage of SLAP repairs within our practice have decreased. The average age of patients undergoing SLAP repair is decreasing, and most SLAP repairs are performed for type II SLAP tears. Level of Evidence Level IV, therapeutic case series.

Purpose The aims of the study were as follows: (1) to perform a systematic review of meta-analyses evaluating platelet-rich plasma (PRP) use at the time of arthroscopic rotator cuff repair surgery and to determine its effect on retear rates and clinical outcomes; (2) to provide a framework for the analysis and interpretation of the best currently available evidence; and (3) to identify gaps within the literature where suggestions for continued investigational efforts would be valid. Methods Literature searches were performed to identify meta-analyses examining arthroscopic rotator cuff repairs augmented with PRP versus control (no PRP). Clinical data were extracted and meta-analysis quality was assessed using the Quality of Reporting of Meta-analyses and Oxman-Guyatt scales. Results Seven meta-analyses met inclusion and exclusion criteria. All were considered as being of similar quality with Quality of Reporting of Meta-analyses scores >15 and Oxman scores of 7. A total of 3,193 overlapping patients treated were included with mean follow-up from 12 to 31 months. When compared with control patients, use of PRP at the time of rotator cuff repair did not result in significantly lower overall retear rates or improved clinical outcome scores. The following postoperative functional scores comparing PRP versus control were reported: Constant (no significant difference demonstrated with PRP use in 5 of 6 reporting meta-analyses), University of California – Los Angeles (no difference, 6 of 6), American Shoulder and Elbow Society (no difference, 4 of 4), and Simple Shoulder Test (no difference, 3 of 5). Subgroup analysis performed by 3 meta-analyses showed evidence of improved outcomes with solid PRP matrix versus liquid, small- and/or medium-sized versus large and/or massive tears, PRP application at the tendon-bone interface versus over tendon, and in the setting of double-row versus single-row rotator cuff. Conclusions The current highest level of evidence suggests that PRP use at the time of arthroscopic rotator cuff repair does not universally improve retear rates or affect clinical outcome scores. However, the effects of PRP use on retear rates trend toward beneficial outcomes if evaluated in the context of the following specific variables: use of a solid PRP matrix; application of PRP at the tendon-bone interface; in double-row repairs; and with small- and/or medium-sized rotator cuff tears. Level of Evidence Level III, systematic review of Level II and III studies.

Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed orthopaedic procedures. Venous thromboembolism is a rare, but potentially serious complication of ACL reconstructions and having a thorough understanding of the potential risk factors could help to minimize the incidence of postoperative deep vein thrombosis or pulmonary embolism. We review some of the literature on the risk factors, diagnosis and treatment of deep vein thrombosis or pulmonary embolism. Although current data does not support the routine use of thromboprophylaxis in all patients undergoing ACL reconstruction, it is important for the clinician to be aware that some consideration should be given for initiating pharmacological prophylaxis in some patients who may be at increased risk for thromboembolic disease.

Immobilization of enzymes on solid supports is crucial in enzymatic reactions and catalysis as it allows reutilization of soluble enzymes and reduces cost. Covalent immobilization of horseradish peroxidise (HRP) on surface-modified mesoporous activated carbon (SMAC) in combination with supercritical carbon dioxide (scCO2) has been investigated in this study. The supercritical medium achieved higher enzyme loading of 83.5% within 3 h compared to 54% when incubated in aqueous phosphate buffer for 30 h. HRP loading in the scCO2 environment was consistently higher for different HRP: SMAC ratios. The significant increase in the rate and quantity of HRP immobilization is attributed to the favourable transport properties of solutes in scCO2 coupled with greater affinity of HRP for the non-polar supercritical solvent which enhances the diffusivity of enzymes into the porous matrix. Immobilized HRP retained enzymatic activity after being reutilized 11 times which indicated that immobilization did not detract from HRP's activity. The immobilized HRP was successfully employed in removing phenol from water via polymerization of dissolved phenol in the presence of hydrogen peroxide (H2O2). The study shows the advantage of using a mesoporous substrate as the immobilization platform for enzymes in combination with scCO2 as the transport medium. It resulted in significant enhancement in the capacity as well as the uptake rate of HRP and resulting in the enhanced phenol removal.

With the awareness of the need for optimal and sustainable use of natural resources, hydrothermal treatment of biomass and biomass waste for energy and resource recovery has received increasing attention. In this context, hydrochars produced by hydrothermal treatment of biomass, which have been traditionally employed as catalyst supports or adsorbents, are now of considerable interest as precursors for activated carbons. Activated carbon produced from hydrochars has been widely used in applications such as energy storage, environmental remediation and resource recovery. Apart from savings in energy and resource conservation, hydrochars are of interest in activated carbon production because they possess unique attributes such as high density of oxygenated functional groups (OFGs) and low degree of condensation which can be tailored to produce activated carbons with specific and desired characteristics. This review aims to integrate the current knowledge on hydrothermal carbonization of biomass waste in the context of resource and energy recovery. Specifically, we bring together recent advances made in this area through a systematic and critical review of the production of activated carbon from hydrochars. Mechanisms involved in the production of hydrochars with different surface characteristics in response to variations in the operating parameters are critically reviewed. The current knowledge gaps and challenges involved in the hydrothermal carbonization of biomass waste are critically evaluated with suggestions for further research.

Background: Tonsillectomy is the oldest surgery performed by otorhinolaryngologists worldwide. Through ages different techniques have been tried to improve the post surgical outcome and reduce morbidity among patients. Aim of the current study was to compare the post-operative pain among the patients undergoing tonsillectomy by cold dissection, bipolar cautery dissection and coblation dissection.Methods: 142 Patients undergoing tonsillectomy in ENT department of TMMC during the period of 3 year were included in the study. Patients were randomly distributed to undergo different techniques of tonsillectomy. The post-operative pain in patients was assessed using the pre-standardized visual analogue pain scale and results were analyzed.Results: No statistically significant difference was found among the groups undergoing tonsillectomy by cold dissection, bipolar dissection and coblator dissection as the p>0.05. The immediate post-operative pain was found to be slightly higher among the group undergoing tonsillectomy by coblator dissection and the analgesics dose needed in the post-operative period remained the same for all for patients of all the three groups.Conclusions: No statistically significant difference was found in the post-operative pain scores of patients undergoing tonsillectomy by CD, BD and CBD techniques.

Background: Aim of the study was to estimate the benefits of having high-resolution computed tomography (HRCT) of temporal bone on clinically evaluated paediatric patients of acquired cholesteatoma.Methods: A total of 60 patients of paediatric age group (2-18 years) who were diagnosed with active squamosal type of chronic otitis media were selected for the study. HRCT of temporal bone was done in all the patients and findings were recorded.Results: Most patients were in the age group of 11-15 years (46.6%). Findings of pars tensa were subtotal perforation in 2 patients (3.3%), small central perforation in 8 patients (13.3%) and postero-superior marginal perforation in 12 patients (20%). Pars flaccida retraction pocket with cholesteatoma was seen in 31 patients (51.6%) and perforation with cholesteatoma in 13 patients (21.6%). Scutum erosion was seen in 31 patients (51.6%), ossicular erosion in 12 patients (20%) and facial nerve paralysis in 2 patients (3.3%). On HRCT temporal bone we found soft tissue density in middle ear in 60 patients (100%), soft tissue density in mastoid in 53patients (88.3%), osscicular erosion in 54 patients (90%), scutum erosion in 46 patients (76.6%), facial nerve canal dehiscence in 5 patients (8.3%), semicircular canal dehiscence in 2 patients (3.3%) and dural plate dehiscence in 11 patients (18.3%).Conclusions: HRCT of temporal bone is helpful in depicting a clearer picture of middle ear cavity structures involved by cholesteatoma and thus helpful in formulating a strategy for further management.

Background: Lesions of the oral cavity are very common among the general population and account for a significant number of patients in the outpatient department of otorhinolaryngology. The lesions of oral cavity can cause varied symptoms like pain, dysphagia, and difficulty in speaking. The lesions can range from simple benign conditions to life threatening malignancies.Methods: This study was conducted in the department of otorhinolaryngology, Teerthanker Mahaveer Medical College and Research Centre from January 2019 till December 2019. All the 256 patients who presented to the outpatient department with lesions in the oral cavity during the given time period were included in the study after getting informed and written consent. Results: Aphthous ulcers were the most common lesion (18.7%) found in this study. Buccal mucosa (50%) and anterior 2/3rd of tongue (34.3%) were the most common sites involved. Total of 204/256 (79.6%) patient had some form of addiction which included both smoked and smokeless form of tobacco as the most common type of addiction. Among the tobacco smokers, 24/80 (30%) had pre malignant and malignant lesions while among tobacco chewers 37/76 (48.6%) had pre malignant and malignant lesions.Conclusions: Lesions of the oral cavity are common among Indian population due to high prevalence of tobacco addiction. A thorough history taking and examination can detect premalignant and malignant lesions at an early stage, so that timely treatment can reduce the mortality rates in such patients.

Background: The fractures of the thoracolumbar junction are the most common injuries of the vertebral column. Fall from a height and road traffic accidents are the main causes of injury. The present study aims to evaluate the functional, neurological and radiological outcome of the posterior decompression and instrumented fusion in operated patients with thoracolumbar fractures.Methods: In this retrospective and prospective study, a cohort of 30 patients with thoracolumbar fractures, classified by thoracolumbar injury classification and severity (TLICS) scoring system, underwent posterior decompression and pedicle screw fixation from January 2013 to August 2018 were included. Patients were assessed functionally (ODI score), neurologically (MRC grading) and radiologically (kyphotic angle) preoperatively and at 6 weeks, 3 months, 6 months and 12 months post-operatively.Results: The mean ODI score improved from 87.40 pre-operatively to 13.33 at final follow-up (p value 0.001). The mean kyphotic angle decreased from 24.37 degrees preoperatively to 9.87 degrees postoperatively (p value 0.001) with mean loss of correction of 1.16 degrees at final follow-up. Hip flexors and knee extensors improved from a mean preoperative value of 2.60 to 4.83 at final follow-up (p value 0.001). Similarly, ankle dorsiflexors, long toe extensors and ankle plantar flexors improved from mean preoperative value of 2.53, 2.50 and 2.60 to 3.93, 3.80 and 4.73 at final follow-up, respectively (p value 0.001).Conclusions: Posterior decompression and instrumented fusion is a safe and effective surgical option in patients with thoracolumbar fractures. TLICS scoring system has a prognostic value and helps in determining the prognosis in these patients.

Background: Bucket-handle meniscus tears (BHMT) are often displaced and unstable and comprise nearly 10% of all meniscus tears and commonly affect the young male population. Displacement of the free segment can lead to significant pain and disability, necessitating reduction and surgical treatment. The aim of present prospective longitudinal cohort study was to evaluate the functional outcomes of bucket handle medial meniscus repair along with anterior cruciate ligament (ACL) reconstruction at 2 years follow up.Methods: Between January 2017 to December 2018, 30 patients who underwent ACL reconstruction along with bucket handle medial meniscus repair were included in the study. Meniscus repair was done using the all inside, outside in, inside out or hybrid techniques. All patients were evaluated clinically at pre op and at 2 year follow up using knee injury and osteoarthritis outcome score and compared. Meniscal healing was assessed clinically using Barrett’s criteria.Results: The study comprised 30 patients with a mean age of 27.47 years (range from 13 to 49 years) with 66.67% males. According to clinical examination and Barrett criteria’s the clinical failure rate was 6.67% (2 out of 30 patients) who underwent partial menisectomy later. We also compared functional outcomes of sedentary and active peoplesand also between meniscal repair of less than 3 cm and more than 3 cm’s. There was no statistically significant difference in the functional outcomes in both the groups; however range of motion was significantly higher in tear length 3 cm or less compared to more than 3 cm.Conclusions: Meniscal repair should be aggressively considered in young pa­tients to enhance functional recovery and durability of the knee joint, if the meniscus is reparable.