A comparison of distal femoral locking plates for distal femur fractures: Long working length versus short working length.

OBJECTIVE: To compare long working length distal femoral locking plates with short working length for treating extra-articular distal femur fractures in terms of union and implant failure. METHODS: The randomised controlled trial was conducted at the Lady Reading Hospital, Peshawar, Pakistan, from April 28, 2018, to March 10, 2021, and comprised all adult patients of either gender with extra-articular distal femur fractures who were randomised into two groups. Group A was exposed to long working length, while group B had short working length. Patients in both the groups were followed up regularly for one year for the assessment of fracture union and implant failure. Data was analysed using SPSS 22. RESULTS: In the group of the 61 patients, 30(49.2%) were in group A; 24(80%) males and 6(20%) females with overall mean age of 37.9±9.6 years. The remaining 31(50.8%) were in group B; 26(83.8%) males and 5(16.1%) females with overall mean age of 37.2±1 years. The mean working length in group A was 75±5mm and in group B it was 35±9mm. In group A 28(93.3%) fractures healed, while in group B 19(61.2%) fractures achieved union (p=0.01). Non-union was noted in 2(6.6%) patients in group A and 7(22.5%) in group B (p=0.08). Plate breakage was noted in 3(9.6%) patients and screw breakage in 2(6.4%) patients in group B and none in group A (p=0.0001). CONCLUSIONS: Long working length titanium locking plates were found to be better than short working length in achieving fracture union and avoiding implant failure.

Role of adipose-derived stem cells in wound healing.

Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration.

Intensifying spatially compound heatwaves: Global implications to crop production and human population.

Recent research has provided crucial insights on regional heatwaves, including their causal mechanisms and changes under global warming. However, detailed research on global-scale spatially compound heatwaves (SCHs) (concurrent heatwaves over multiple regions) is lacking. Here, we find statistically significant teleconnections in heatwaves and show that the frequency of global-scale SCHs and their areal extent have increased significantly, which has led to 50 % increase in the population exposed to extreme heat stresses in the two most recent decades. Crop yields were reduced in most of the years of anomalous heatwaves, which often happen during El-Niños. The internal climate variability appears to significantly influence the inter-annual variability of regional and global heatwave extents. Insights gained here are critical in better quantifying heat stress risks inflicted on socioecological systems.

Optimizing control efficiency in discrete-time multi-agent systems via event-triggered containment techniques combining disturbance handling and input delay management.

The goal of this paper is to mitigate disturbances and input delays while optimizing controller actuation updates for discrete-time multi-agent systems through the use of an event-triggered confinement control system, especially in resource-constrained scenarios. This approach when combined with event-triggered control techniques, then every follower in the system adjusts its condition at specified times based on an event-triggered condition that is suggested. The containment control system issue in the presence of disturbances and input delays was tackled by using both decentralized and centralized event-triggered control systems. Using matrix theory and the Lyapunov technique, convergence analysis is conducted to show that the proposed strategy stays free of zeno phenomena. Numerical boosts are used to further illustrate the impact of theoretical results.

"One-step" preparation of thiol-ene clickable PEG-based thermoresponsive hyperbranched copolymer for in situ crosslinking hybrid hydrogel.

A well-defined poly(ethylene glycol) based hyperbranched thermoresponsive copolymer with high content of acrylate vinyl groups was synthesized via a "one-pot and one-step" deactivation enhanced atom transfer radical polymerization approach, which provided an injectable and in situ crosslinkable system via Michael-type thiol-ene reaction with a thiol-modified hyaluronan biopolymer. The hyperbranched structure, molecular weight, and percentage of vinyl content of the copolymer were characterized by gel permeation chromatography and (1)H NMR. The lower critical solution temperature of this copolymer is close to body temperature, which can result in a rapid thermal gelation at 37 °C. The scanning electron microscopy analysis of crosslinked hydrogel showed the network formation with porous structure, and 3D cell culture study demonstrated the good cell viability after the cells were embedded inside the hydrogel. This injectable and in situ crosslinking hybrid hydrogel system offers great promise as a new class of hybrid biomaterials for tissue engineering.

Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in situ cross-linkable hyaluronic acid composite semi-IPN hydrogel.

Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an 'one pot and one step' in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, M(n) = 258 g mol(-1)), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n )= 475 g mol(-1)) and (2-methoxyethoxy) ethyl methacrylate (MEO(2)MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models.

A Review of the First 100 Cases of Laparoscopic Nephrectomy: A Single-Center Experience.

Objective Since 1990, when the first laparoscopic nephrectomy was performed, there has been a dramatic increase in interest in laparoscopic procedures in urological surgeries.The aim of the study was to present our experience with the first 100 cases of laparoscopic nephrectomy at our institute, identify the difficulties encountered, and discuss how to approach the solutions. Materials and methods The data of all patients who underwent laparoscopic nephrectomy between May 2017 and April 2019 (n=100) were reviewed retrospectively. Results A total of 100 patients (49 men and 51 women), with a mean age of 34.1 ± 15.1 years, underwent laparoscopic nephrectomy. The mean operative time was 108 min (IQR, 45-240). The operative time was significantly reduced with the surgeons' experience. Of 100 cases, only four were converted to open surgery because of bleeding from the renal bed area, strong adhesions from previous surgeries, or morbid obesity. Of 100 patients, 30 were allowed intake on the same operative day while 70 were allowed on the first postoperative day. Intravenous and oral analgesics were discontinued on the second postoperative day in 81 patients. Conclusion The learning curve in our series of cases is comparable to a very similar studywith reduced operative time, reduced blood loss, and fewer complications when compared to open nephrectomy. In addition, setups with minimal previous laparoscopic units can initiate laparoscopic procedures with minimal risk to the patient.

Recent changes in heatwaves and maximum temperatures over a complex terrain in the Himalayas.

The temperature response to anthropogenic global warming and forest cover changes is dependent on regional climatic characteristics. It is challenging to segregate the impacts of the two anthropogenic changes on local temperatures and heatwaves over complex mountainous regions. Here we present estimates of regional and local heat stress responses to the recent global climate change and local forest cover loss in complex terrain in the Himalayas using a satellite-based high-resolution land-surface temperature dataset. We find large-scale decreasing trends in the observed frequency of heatwaves and heat days, and localized increases in urbanized and high-elevation regions. Our results show large-scale significant decreasing trends in annual maximum and mean surface temperatures over the period 2003-2019. In locations that have witnessed large-scale forest losses, the declines in the surface temperatures were steeper compared to no-loss regions. We develop a regional multiple linear regression model to estimate the regional and local temperature responses to global climatic change and to segregate them from the response to forest cover losses. Our model estimates a regional decrease of about 2.0 °C in annual maximum temperature over the recent 2003-2019 period, which is locally modulated by the extent of urbanization, forest cover, and elevation. At the locations of intense deforestation, our model successfully predicts a steeper decrease in maximum surface temperature, and estimates the temperature response due to forest loss, after controlling for elevation and initial forest cover. The local cooling effect due to deforestation was reaffirmed by comparing the regions with contrasting forest cover losses. The results suggest that forest clearing amplifies the anthropogenic climate change over the region.

Doppler-Assessed Ureteric Jet Frequency: A Valuable Predictor of Ureteric Obstruction.

OBJECTIVES: To compare ureterovesical jet frequency in non-obstructed versus obstructed ureter secondary to ureteric stone using ultrasonography in patients presenting with ureteral stones. STUDY DESIGN:  Cross-sectional prospective study. Place of study and duration: Urology Department, The Kidney Centre Post Graduate Training Institute from May 16 to November 15, 2019. METHODS: This study included 97 patients having presented in the emergency department with acute renal colic and were diagnosed as having ureteral stones on a non-contrast-enhanced computed tomography (NCCT). The ureteric jet frequency was measured by Doppler ultrasonography by our radiologist with the Hitachi Aloka F-37 ultrasound machine after they underwent CT. Patients were asked to drink 750-1000 ml of liquids 15-20 minutes before their ultrasonographic examination of both kidneys, ureters, and urinary bladder. The kidney size (length and width) and presence/absence of hydronephrosis were evaluated by grayscale ultrasound. Then, with the help of color Doppler ultrasonography, the frequency of the ureteric jet was recorded. RESULTS: The patient's mean age was 46.66 ± 3.21 years ranging from 37 to 56 years. There were 58 (59.8%) male and 39 (40.2%) female cases. The mean cumulative stone size was 9.77 ± 2.65 mm. According to stone location, 44 (45.4%) cases had upper ureteric, 24 (24.7%) cases had mid ureteric, and 29 (29.9%) cases had lower ureteric stone. The mean obstructive side jet frequency was 0.70/min ± 0.49, and the non-obstructive side jet frequency was 2.89/min ± 1.29 (P < 0.05). CONCLUSIONS: The mean obstructive side jet frequency was 0.70 ± 0.49/min, which, if we compare to the non-obstructed normal ureter, is significantly less. Hence, color Doppler ultrasonography can be helpful to patients who were previously diagnosed with ureteral stones on NCCT to see if their stone has passed. This can be a very cost-effective modality especially in resource-poor countries where repeat CT can be very expensive. The results from this study can also be used in a specific population (i.e., pregnancy) where the use of imaging modalities that involve ionizing radiation is prohibited.

Percutaneous Nephrolithotomy in a Previously Operated Kidney.

OBJECTIVE: To ascertain the safety and efficacy of percutaneous nephrolithomy in patients with previous open renal surgery. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Kidney Centre Postgraduate Training Institute, Karachi from January to December 2018. METHODOLOGY: Patients with previous open renal surgery underwent percutaneous nephrolithomy during study period (Group A). Equal number of percutaneous nephrolithomy patients without previous open surgery taken as controls (Group B). Safety was defined in terms of 'blood loss' as change in hemoglobin (HB) level and 'blood transfusion,' while efficacy was defined in terms of 'stone clearance' and were compared between both the groups. RESULTS: There were a total of 87 patients. Both groups had comparative gender ratio [p = 0.858]. Mean age [p = 0.132] and BMI [p = 0.879] of patients in both groups was not significantly different from each other. Both groups showed no statistically significant difference in terms of values of stone size [p = 0.186], stone laterality [p = 0.437] stone location [p = 0.949], preoperative Hb [p = 0.095], postoperative Hb [p = 0.423] and change in Hb (indicating blood loss, p = 0.398). Puncture levels were significantly different among both groups (supracostal puncture in 18 and 36 patients; infracostal puncture in 63 and 51 patients in groups A and B, respectively, p = 0.006), while operative time [p = 0.787], calyx punctured [p = 0.051], double puncture [p = 0.787], nephrostomy tube [p = 0.288] were statistically not different among groups. Similar number of patients demonstrated residual stones [p = 0.773], along with residual stone sizes [Group A (0.5; 0.5) and Group B (0.65; 0.38)] [p = 0.445]. Intra- and postoperative complications like blood transfusion [p = 0.700] and fever [p = 1.000] along with hospital stay [p = 0.614] were comparable among groups. CONCLUSION: Percutaneous nephrolithomy is safe and effective in previously operated kidneys despite the possibility of calyceal anatomy distortion and scarring. Key Words: Percutaneous nephrolithotomy, Open surgery, Kidney calculi.

Pharmacogenetics of treatments for pancreatic cancer.

Introduction: Despite clinical efforts, pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The scarcity of effective therapies can be reflected by the lack of reliable biomarkers to adapt anticancer drugs prescription to tumors' and patients' features. Areas covered: Pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best matches individual and tumor genetic profile, but it has not yet led to gains in outcome. This review describes PDAC pharmacogenetics findings, critically reappraising studies on polymorphisms and -omics profiles correlated to response to gemcitabine, FOLFIRINOX, and nab-paclitaxel combinations, as well as limitations of targeted therapies. Further, we question whether personalized approaches will benefit patients to any significant degree, supporting the need of new strategies within well-designed trials and validated genomic tests for treatment decision-making. Expert opinion: A major challenge in PDAC is the identification of subgroups of patients who will benefit from treatments. Minimally-invasive tests to analyze biomarkers of drug sensitivity/toxicity should be developed alongside anticancer treatments. However, progress might fall below expectations because of tumor heterogeneity and clonal evolution. Whole-genome sequencing and liquid biopsies, as well as prospective validation in selected cohorts, should overcome the limitations of traditional pharmacogenetic approaches.

Frequency of hepatopulmonary syndrome in cirrhotic patients.

OBJECTIVE: To determine the frequency of Hepatopulmonary Syndrome (HPS) in patients with cirrhosis of the liver. STUDY DESIGN: Observational cross-sectional study. PLACE AND DURATION OF STUDY: Department of Gastroenterology and Hepatology, Shaikh Zayed Hospital, Lahore, from April 2005 to March 2006. PATIENTS AND METHODS: Fifty consecutive patients admitted with liver cirrhosis were recruited. Twelve patients were excluded due to inadequate echocardiography image quality and inability to perform lung function tests. The diagnosis of cirrhosis was made on clinical, biochemical, serological and metabolic workup, ultrasound abdomen or liver biopsy. Complete blood count, liver function tests, prothrombin time, serum albumin, electrocardiography, chest radiograph, transthoracic contrast echocardiography, arterial blood gas analysis and pulmonary function tests (FEV1) were performed. Results were analyzed as percentages. Chi-square test of proportions and t-test were applied. RESULTS: Total patients evaluated were 38. Mean age was 47.92 +/- 11.38 years, with male (68.4%) to female (31.6%) ratio of 2.1:1. The commonest cause of cirrhosis was hepatitis C (71.1%). Out of the 38 patients, 11 (28.9%) had HPS including 5 (13.2%) with overt HPS and 6 (15.8%) with subclinical HPS. All patients with HPS had hepatitis C with Child-Pugh-Turcotte (CPT) class C. Factors associated with HPS were digital clubbing, arterial hypoxemia and intrapulmonary vascular dilatations (p=0.02, 0.05 and 0.000 respectively). CONCLUSION: In this study, 28.9% patients with cirrhosis of the liver had HPS. All belonged to child class C due to hepatitis C. Digital Clubbing, arterial hypoxemia and intrapulmonary vascular dilatations were important features of hepatopulmonary syndrome.

Performance of an in situ formed bioactive hydrogel dressing from a PEG-based hyperbranched multifunctional copolymer.

Hydrogel dressings have been widely used for wound management due to their ability to maintain a hydrated wound environment, restore the skin's physical barrier and facilitate regular dressing replacement. However, the therapeutic functions of standard hydrogel dressings are restricted. In this study, an injectable hybrid hydrogel dressing system was prepared from a polyethylene glycol (PEG)-based thermoresponsive hyperbranched multiacrylate functional copolymer and thiol-modified hyaluronic acid in combination with adipose-derived stem cells (ADSCs). The cell viability, proliferation and metabolic activity of the encapsulated ADSCs were studied in vitro, and a rat dorsal full-thickness wound model was used to evaluate this bioactive hydrogel dressing in vivo. It was found that long-term cell viability could be achieved for both in vitro (21days) and in vivo (14days) studies. With ADSCs, this hydrogel system prevented wound contraction and enhanced angiogenesis, showing the potential of this system as a bioactive hydrogel dressing for wound healing.

Encapsulation and 3D culture of human adipose-derived stem cells in an in-situ crosslinked hybrid hydrogel composed of PEG-based hyperbranched copolymer and hyaluronic acid.

INTRODUCTION: Cell therapy using adipose-derived stem cells has been reported to improve chronic wounds via differentiation and paracrine effects. One such strategy is to deliver stem cells in hydrogels, which are studied increasingly as cell delivery vehicles for therapeutic healing and inducing tissue regeneration. This study aimed to determine the behaviour of encapsulated adipose-derived stem cells and identify the secretion profile of suitable growth factors for wound healing in a newly developed thermoresponsive PEG-hyaluronic acid (HA) hybrid hydrogel to provide a novel living dressing system. METHODS: In this study, human adipose-derived stem cells (hADSCs) were encapsulated in situ in a water-soluble, thermoresponsive hyperbranched PEG-based copolymer (PEGMEMA-MEO2MA-PEGDA) with multiple acrylate functional groups in combination with thiolated HA, which was developed via deactivated enhanced atom transfer radical polymerisation of poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, Mn = 475), 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) and poly(ethylene glycol) diacrylate PEGDA (Mn = 258). hADSCs embedded in the PEGMEMA-MEO2MA-PEGDA and HA hybrid hydrogel system (P-SH-HA) were monitored and analysed for their cell viability, cell proliferation and secretion of growth factors (vascular endothelial growth factor, transforming growth factor beta and placental-derived growth factor) and cytokines (IFNγ, IL-2 and IL-10) under three-dimensional culture conditions via the ATP activity assay, alamarBlue® assay, LIVE/DEAD® assay and multiplex ELISA, respectively. RESULTS: hADSCs were successfully encapsulated in situ with high cell viability for up to 7 days in hydrogels. Although cellular proliferation was inhibited, cellular secretion of growth factors such as vascular endothelial growth factor and placental-derived growth factor production increased over 7 days, whereas IL-2 and IFNγ release were unaffected. CONCLUSION: This study indicates that hADSCs can be maintained in a P-SH-HA hydrogel, and secrete pro-angiogenic growth factors with low cytotoxicity. With the potential to add more functionality for further structural modifications, this stem cell hydrogel system can be an ideal living dressing system for wound healing applications.