International Consensus Recommendations for Safe Use of LAMS for On- and Off-Label Indications Using a Modified Delphi Process.

INTRODUCTION: The study aimed to develop international consensus recommendations on the safe use of lumen-apposing metal stents (LAMSs) for on- and off-label indications. METHODS: Based on the available literature, statements were formulated and grouped into the following categories: general safety measures, peripancreatic fluid collections, endoscopic ultrasound (EUS)-biliary drainage, EUS-gallbladder drainage, EUS-gastroenterostomy, and gastric access temporary for endoscopy. The evidence level of each statement was determined using the Grading of Recommendations Assessment, Development, and Evaluation methodology.International LAMS experts were invited to participate in a modified Delphi process. When no 80% consensus was reached, the statement was modified based on expert feedback. Statements were rejected if no consensus was reached after the third Delphi round. RESULTS: Fifty-six (93.3%) of 60 formulated statements were accepted, of which 35 (58.3%) in the first round. Consensus was reached on the optimal learning path, preprocedural imaging, the need for airway protection and essential safety measures during the procedure, such as the use of Doppler, and measurement of the distance between the gastrointestinal lumen and the target structure. Specific consensus recommendations were generated for the different LAMS indications, covering, among others, careful patient selection, the preferred size of the LAMS, the need for antibiotics, the preferred anatomic location of the LAMS, the need for coaxial pigtail placement, and the appropriate management of LAMS-related adverse events. DISCUSSION: Through a modified international Delphi process, we developed general and indication-specific experience- and evidence-based recommendations on the safe use of LAMS.

Safety and adverse events of EUS-guided gallbladder drainage using lumen-apposing metal stents and percutaneous cholecystostomy tubes: a systematic review and meta-analysis.

BACKGROUND AND AIMS: EUS-guided gallbladder drainage using lumen-apposing metal stents (EUS-GBD-LAMSs) and percutaneous cholecystostomy for gallbladder drainage (PTGBD) are the alternative treatment modalities in high-risk surgical patients with acute cholecystitis (AC). The aim of this study was to compare the safety of these procedures for AC in surgically suboptimal candidates. METHODS: Six studies compared the 2 groups' early, delayed, and overall adverse events; they also compared length of hospital stay, re-interventions, and re-admissions rate. A random effect model calculated odds ratios (ORs) with a 95% confidence interval (CI). RESULTS: The 2 groups had similar early adverse events; however, EUS-GBD-LAMS was associated with a lower rate of delayed (OR, .21; 95% CI, .07-.61; P ≤ .01) and overall (OR, .43; 95% CI, .30-.61; P ≤ .01) adverse events. Patients with EUS-GBD-LAMSs had a shorter hospital stay than PTGBD. CONCLUSIONS: EUS-GBD-LAMS is a safer option than PTGBD and is associated with a shorter hospital stay in nonsurgical candidates with AC.

Adjuvant Radiofrequency Ablation Along With Stenting Versus Stenting Alone for Biliary Tree Drainage in Patients With Malignant Biliary Strictures: A Systemic Review and Meta-analysis.

OBJECTIVE: This metanalysis aims to assess the efficacy and safety of biliary stenting along with radiofrequency ablation compared with stents alone to treat malignant biliary obstruction (MBO) due to extrahepatic biliary strictures secondary to cholangiocarcinoma, pancreatic cancer, and metastatic cancer. METHODS: A systemic search of major databases through April 2022 was done. All original studies were included comparing radiofrequency ablation with stenting versus stenting alone for treating malignant biliary strictures. The primary outcomes of interest were the difference in the mean stent patency and overall survival (OS) days between the 2 groups. The secondary outcome was to compare the adverse events of the 2 groups. The mean difference in the stent patency and OS days was pooled by using a random-effect model. We calculated the odds ratio to compare the adverse events between the 2 groups. RESULTS: A total of 13 studies with 1339 patients were identified. The pooled weighted mean difference in stent patency was 43.50 days (95% CI, 25.60-61.41), favoring the RFA plus stenting. Moreover, the pooled weighted mean difference in OS was 90.53 days (95% CI, 49.00-132.07), showing improved survival in the RFA group. Our analysis showed no statistically significant difference in adverse events between the 2 groups OR 1.13 (95% CI, 0.90-1.42). CONCLUSION: Our analysis showed that RFA, along with stent, is safe and is associated with improved stent patency and overall patient survival in malignant biliary strictures. More robust prospective studies should assess this association further.

Pancreatic Walled-Off Necrosis: Cross-Sectional Imaging Depiction of Debris Predicts the Success of Endoscopic Drainage Using Lumen-Apposing Metal Stents.

INTRODUCTION: The use of endoscopic ultrasound (EUS)-guided transmural stent placement for pancreatic walled-off necrosis (WON) drainage is widespread. This study retrospectively analyzed imaging parameters predicting the outcomes of WON endoscopic drainage using lumen-apposing metal stents (LAMS). METHODS: This study analyzed the data of 115 patients who underwent EUS-guided debridement using LAMS from 2011 to 2015. Pre-intervention CT or MRI was used to analyze the total volume of WON, percentage of debris, multilocularity, and density. Success measures included technical success, the number of endoscopic sessions, the requirement of percutaneous drainage, long-term success, and recurrence. RESULTS: The primary cause of pancreatitis was gallstones (50.4%), followed by alcohol (27.8%), hypertriglyceridemia (11.3%), idiopathic (8.7%), and autoimmune (1.7%). The mean WON size was 674 mL. All patients underwent endoscopic necrosectomy, averaging 3.1 sessions. Stent placement was successful in 96.5% of cases. Procedural complications were observed in 13 patients (11.3%) and 6 patients (5.2%) who needed additional percutaneous drainage. No patients reported recurrent WON posttreatment. Univariate analysis indicated a significant correlation between debris percentage and the need for additional drainage and long-term success (p < 0.001). The number of endoscopic sessions correlated significantly with debris percentage (p < 0.001). CONCLUSION: Pre-procedural imaging, particularly debris percentage within WON, significantly predicts the number of endoscopic sessions, the need for further percutaneous drainage, and overall long-term success.

Knowledge and attitude towards the use of pain medications according to WHO cancer pain analgesic ladder in tertiary care hospitals of Pakistan.

To assess the knowledge and attitude of practicing physicians and surgeons towards the use of pain medication according to the World Health Organisation cancer pain analgesic ladder, the current study was conducted at tertiary care hospitals of the four provinces of Pakistan. Professionals having experience of treating cancer patients for >2 years were included. Data was collected using a self-administered questionnaire sent to each participant using Google Forms. Of the 630 physicians approached, 133(21%) responded. Of them, 74(55.64%) participants were familiar with the World Health Organisation analgesic ladder. There was a significant difference in the frequency of using the ladder based on age (p<0.05). Most participants 31(23%) reported the nonavailability of the recommended drugs as the reason for not following the analgesic ladder. There is a strong need to educate physicians and surgeons about the World Health Organisation analgesic ladder, and to make strategies to improve opioid availability in Pakistan.

Age is a predictor of elbow stiffness after type III or IV supracondylar humerus fractures.

PURPOSE: Supracondylar humerus (SCH) fractures account for approximately 30% of injuries for those younger than 7 years of age (Cheng et al. in J Pediatr Orthop 19:344-350, 1999). Recent studies examining the association of patient age and SCH fracture outcomes have provided conflicting findings. The purpose of this study is to investigate SCH fracture outcomes in children at different ages of skeletal development. METHODS: Retrospective review of a Level I pediatric trauma center between 2010 and 2014 was conducted. 190 patients with SCH fractures, age < 14 years, fracture type Gartland III or IV (AO/OTA 13-M 3.1 III and IV) were included. Patients were sorted into age groups: < 2 years, 4-6 years, and > 8 years. Patients were treated with either a closed or open reduction with percutaneous fixation. Clinical outcomes including postoperative elbow range of motion, nerve palsy, compartment syndrome, infection, and cubitus varus were assessed. RESULTS: Patients in younger age groups were more likely to obtain postoperative full elbow flexion (< 2 years = 77%; 4-6 years = 66%; > 8 years = 43%) and full elbow extension (< 2 years = 96%; 4-6 years = 88%; > 8 years = 64%). Age was a significant predictor of nerve palsy on admission, mean operative time (< 2 years = 21.8 min; 4-6 years = 43.0 min; > 8 years = 80.7 min), and mean fluoroscopy time (< 2 years = 22.9 s; 4-6 years = 59.5 s; > 8 years = 171.9 s). There were no differences in rates of open reduction, compartment syndrome, pin tract infection, cubitus varus, or reoperation among groups. CONCLUSION: Increasing age is associated with increased elbow stiffness after percutaneous fixation of Gartland Type III and Type IV SCH fractures. Older patients with SCH fractures may benefit from formal rehabilitation. LEVEL OF EVIDENCE: III.

Lateralizing calcaneal osteotomy performed with a percutaneous burr results in a significantly lower increase in tarsal tunnel pressure.

PURPOSE: Tarsal tunnel syndrome is well documented following lateralizing calcaneal osteotomy to manage varus hindfoot deformity. Traditionally, calcaneal osteotomy is performed with an oscillating saw. No studies have investigated the effect of alternative surgical techniques on postoperative tarsal tunnel pressure. The purpose of this study was to investigate the difference in tarsal tunnel pressures following lateralizing calcaneal osteotomy performed using a high-torque, low-speed "minimally invasive surgery" (MIS) Shannon burr versus an oscillating saw. METHODS: Lateralizing calcaneal osteotomy was performed on 10 below-knee cadaveric specimens. This was conducted on 5 specimens each using an oscillating saw (Saw group) or MIS burr (Burr group). The calcaneal tuberosity was translated 1 cm laterally and transfixed using 2 Kirschner wires. Tarsal tunnel pressure was measured before and after osteotomy via ultrasound-guided percutaneous needle barometer. Mean pre/post-osteotomy pressures were compared between groups. Differences were analyzed using Student's t test. RESULTS: The mean pre-procedure tarsal tunnel pressure was 25.8 ± 5.1 mm Hg in the Saw group and 26.4 ± 4.3 mm Hg in the Burr group (p = 0.85). The mean post-procedure pressure was 63.4 ± 5.1 in the Saw group and 47.8 ± 4.3 in the Burr group (p = 0.01). Change in tarsal tunnel pressure was significantly lower in the Burr group (21.4 ± 4.5) compared to the Saw group (37.6 ± 12.5) (p = 0.03). The increase in tarsal tunnel pressure was 43% lower in the Burr group. CONCLUSION: In this cadaveric study, tarsal tunnel pressure increase after lateralizing calcaneal osteotomy was significantly lower when using a burr versus a saw. This is likely because the increased width ("kerf") of the 3 mm MIS burr, compared to the submillimeter saw blade width, causes calcaneal shortening. Given the smaller increase in tarsal tunnel pressure, using the MIS burr for lateralizing calcaneal osteotomy may decrease the risk of postoperative tarsal tunnel syndrome. Future research in vivo should explore this.

Mesh Type With Ventral Hernia Repair: A Systematic Review and Meta-analysis of Randomized Trials.

INTRODUCTION: Synthetic mesh is widely utilized for clean ventral hernia repair; however, it is unclear if synthetic mesh provides the same benefits with high-risk patients or during contaminated cases. Many surgeons use biologic mesh in these settings, but there is little evidence to support this practice. Our objective was to compare the clinical outcomes of utilizing biologic mesh versus synthetic mesh during ventral hernia repair. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a review of the literature was conducted using Cochrane library, EMBASE, Clinicaltrials.gov, and PubMed for randomized controlled trials published that compared biologic versus synthetic mesh during ventral hernia repair. The primary outcome was major complications defined as deep or organ space surgical site infection, reoperations, and hernia recurrences. RESULTS: Of 1889 manuscripts screened, four publications were included. The four studies included a total of 758 patients, with 381 receiving biologic mesh and 377 receiving synthetic mesh. Compared to biologic mesh, synthetic mesh had lower rates of major complications (38.6% versus 23.4, risk ratio = 0.55, 95% confidence interval = 0.35 to 0.86, P = 0.009) and hernia recurrence (24.5 % versus 10.3%, risk ratio = 0.44, 95% confidence interval = 0.28 to 0.69, P = 0.004). In addition, there was a lower percentage of surgical site infection and reoperation in the synthetic mesh group. CONCLUSIONS: Contrary to current surgical teaching, placement of permanent synthetic mesh into a contaminated field yielded rates of complications that were comparable or reduced compared to biologic mesh.

Arctic freshwater impact on the Atlantic Meridional Overturning Circulation: status and prospects.

Arguably, the most conspicuous evidence for anthropogenic climate change lies in the Arctic Ocean. For example, the summer-time Arctic sea ice extent has declined over the last 40 years and the Arctic Ocean freshwater storage has increased over the last 30 years. Coupled climate models project that this extra freshwater will pass Greenland to enter the sub-polar North Atlantic Ocean (SPNA) in the coming decades. Coupled climate models also project that the Atlantic Meridional Overturning Circulation (AMOC) will weaken in the twenty-first century, associated with SPNA buoyancy increases. Yet, it remains unclear when the Arctic anthropogenic freshening signal will be detected in the SPNA, or what form the signal will take. Therefore, this article reviews and synthesizes the state of knowledge on Arctic Ocean and SPNA salinity variations and their causes. This article focuses on the export processes in data-constrained ocean circulation model hindcasts. One challenge is to quantify and understand the relative importance of different competing processes. This article also discusses the prospects to detect the emergence of Arctic anthropogenic freshening and the likely impacts on the AMOC. For this issue, the challenge is to distinguish anthropogenic signals from natural variability. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.

Genome Editing and Fatty Liver.

Fatty liver disease is characterized as nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Fatty liver disease is one of the most common causes of chronic liver disease worldwide among adults and children. It is characterized by excessive fat accumulation in the liver cells. It has a genetically heterogenous background with complex pathogenesis and progressions and is accompanied by significant morbidity, mortality, and healthcare costs. NAFLD's risk factors include metabolic syndrome, abdominal obesity, type 2 diabetes, and atherogenic dyslipidemia. ALD is associated with the excessive consumption of alcohol. Here, we describe the functions of various proteins encoded by gene variants contributing to the pathogenesis of nonalcoholic fatty liver disease and alcoholic fatty liver disease. Advancements in genome engineering technology have generated various in vivo and in vitro fatty liver disease models reflecting the genetic abnormalities contributing toward fatty liver disease. We will discuss currently developed different ALD and NAFLD models using the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) genome editing tool.Furthermore, we will also discuss the salient features of CRISPR/Cas9 editing technology and Cas9 variants such as prime and base editors to replicate genetic topographies linked specifically to ALD and NAFLD. The advantages and limitations of currently available genome delivery methods necessary for optimal gene editing will also be discussed in this review. This review will provide the essential guidance for appropriate genome editing tool selection and proper gene delivery approaches for the effective development of ALD and NAFLD models, leading to the development of clinical therapeutics for fatty liver disease.

Pain assessment in intensive care units of a low-middle income country: impact of the basic educational course.

BACKGROUND: Patients admitted to ICU usually have moderate-to-severe pain at rest and during care-related activities. The "Critical Care Pain Observation Tool (CPOT)" is a reliable and validated objective assessment tool for those patients who cannot self-report pain in ICU. The objectives of the educational course were to assess the baseline knowledge, and practice of pain assessment in critically ill patients and reassess the same in all participants of the course by comparing the results of pre and post-test. METHODS: The educational course of six hours of contact time on the use of CPOT for pain assessment in ICU patients was designed and conducted by the authors after approval from the Ethics Review Committee, Aga Khan University. This educational course was delivered at five different tertiary care hospitals in the Sindh province of Pakistan. A pre-test consisting of 25 true/false multiple-choice questions was conducted at the beginning of the course to assess the baseline knowledge, and practice of participants regarding pain assessment in critically ill patients and the same test was taken at the end of the course. RESULTS: A total of 205 critical care physicians and nursing staff attended the courses. Both pre-test and post-test were completed by 149 (72.6%) participants, of which 53 (35.6%) were female and 96 (64.4%) were male. The mean pre-test score of participants was 57.83 ± 11.86 and the mean post-test score of participants was 67.43 ± 12.96 and this was statistically significant (p = < 0.01). In univariate analysis, the effect of training was significantly higher in the female gender (p = 0.0005) and in those participants, who belong to the metropolitan city (p = 0.010). In multivariate analysis, participants from non-metropolitan cities showed less improvement in post-test scores compared to those who come from the metropolitan city (p = 0.038). CONCLUSIONS: The participating physicians and nurses showed a positive impact on the knowledge and clinical skills regarding pain assessment in CIPs. The participants from hospitals in metropolitan cities showed a significant improvement over those who were from non-metropolitan cities.

Modernizing Our Understanding of Total Hip Arthroplasty in the Pediatric and Young Adult Patient: A Single-center Experience.

INTRODUCTION: Pediatric hip disorders represent a broad range of pathology and remain a significant source of morbidity for children and young adults. Surgical intervention is often required for joint preservation, but when salvage is not possible, joint replacement may be indicated to eliminate pain and preserve function. Although there have been significant updates in the management of both pediatric hip disease and the field of total hip arthroplasty (THA), there is a paucity of literature reflecting advancements in the area of pediatric and young adult (PYA) arthroplasty. No study has investigated the impact of approach on outcomes after PYA THA. The purpose of this study is to describe the indications, techniques, and early outcomes of THA in the PYA population in a modern practice setting. METHODS: We performed a retrospective descriptive analysis of all patients undergoing primary THA performed at a tertiary care children's hospital from 2004 to 2019. Ninety-three hips in 76 patients were evaluated. Demographics, intraoperative variables, postoperative pain and function ratings, and complication and revision rates were collected. RESULTS: Eighty-five hips in 69 patients were included. Patients were aged 12 to 23 years old, with males and females represented equally (33 vs. 36, respectively). The most common cause of hip pain was avascular necrosis (AVN, 56/85, 66%), most commonly due to slipped capital femoral epiphysis (13/56, 23%) idiopathic AVN (12/56, 21%), and chemotherapy (12/56, 21%). Half of all hips had been previously operated before THA (43/85). Thirty-six procedures were performed via the posterolateral approach (36/85, 42%), 33 were performed via direct anterior approach (33/85, 39%), and 16 were performed via the lateral approach (LAT, 16/85, 19%). At final follow-up, 98% (83/85) of patients had complete resolution of pain, 82% (70/85) had no notable limp, and 95% (81/85) had returned to all activities. There were 6 complications and 1 early revision. Average Hip disability and Osteoarthritis Outcomes Score for Joint Replacement scores increased by 37 points from 56 to 93. The overall revision-free survival rate for PYA THA was 98.8% (at average 19-mo follow-up). CONCLUSIONS: Modern PYA THA is dissimilar in indications and surgical techniques to historic cohorts, and conclusions from prior studies should not be generalized to modern practice. In our practice, PYA patients most commonly carry a diagnosis of AVN, and THA can be performed with modern cementless fixation with large cup and head sizes and ceramic-on-cross-linked polyethylene bearings utilizing any approach. Further study is required to better characterize middle-term and long-term results and patient-reported outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV-retrospective case series.

The analgesic efficacy of ultrasound-guided transversus abdominis plane block vs. local anesthetic infiltration technique in major gynecologic surgery: A randomized controlled trial.

Background and Aim: Transversus abdominis plane (TAP) block and local anesthetic infiltration (LAI) technique are used as part of the multimodal analgesic regimen after abdominal surgery. Postoperative opioid consumption and analgesic efficacy was compared using TAP and LAI techniques in patients undergoing gynecologic surgery in a randomized, controlled clinical trial. Material and Methods: Total of 135 patients scheduled for major gynecological surgeries were allocated into three groups: group T received bilateral TAP block with bupivacaine 0.25%; group I received LAI with 0.25% bupivacaine with epinephrine 5 µ/mL in the peritoneum and abdominal wall, and group C was control group. Anesthesia and postoperative analgesia were standardized. Outcome measures were cumulative and rescue tramadol consumption, numerical rating score (NRS) for pain and side effects in post-anesthesia care unit (PACU) at 4, 8, 12 hours postoperatively. Results: Tramadol consumption, need for rescue analgesia, and NRS for pain between three groups at 4, 8, and 12 hours postoperatively had no statistically significant difference (P < 0.05). In PACU, median tramadol consumption used for rescue analgesia between group T (15 (15-30)) and group C (30 (15-45)) (P = 0.035), and between group T (15 (15-30)) and group I (30 (15-52)) was statistically significant (P = 0.034). In PACU, the percentage of patients having NRS >4 on movement in group C (72%) compared to group T (46.5%) and group I (46.5%) was significant (P = 0.034). No statistically significant difference was observed in the incidence of side effects among study groups (P > 0.05). Conclusion: Except for the immediate postoperative period, neither TAP block nor LAI had added benefit to the multimodal analgesia regimen in patients undergoing gynecological surgeries.

Femoral tunnel malposition is the most common indication for revision medial patellofemoral ligament reconstruction with promising early outcomes following revision reconstruction: a systematic review.

PURPOSE: The purpose of this study was to identify the causes of failure of previous medial patellofemoral ligament reconstruction (MPFL-R), and to furthermore report the surgical techniques available for MPFL revision surgery. METHODS: Four databases [PubMed, Ovid (MEDLINE), Cochrane Database, and EMBASE] were searched until September 29, 2020 for human studies pertaining to revision MPFL. Two reviewers screened the literature independently and in duplicate. Methodological quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria, or the CAse REport guidelines (CARE), where appropriate. RESULTS: Fourteen studies (one level II, one level III, two level IV, ten level V) were identified. This search resulted in a total of 76 patients with a mean age (range) of 22 (14-39) years. The patients were 75% female with a mean (range) time to revision of 24.1 (1-60) months and mean (range) follow-up of 36.2 (2-48) months. The most common indication for revision surgery was malpositioning of the femoral tunnel (38.1%), unaddressed trochlear dysplasia (18.4%), patellar fracture (11.8%). Femoral tunnel malposition was typically treated via revision MPFL-R with quadriceps tendon or semitendinosus autograft and may retain the primary graft if fixation points were altered. Unaddressed trochlear dysplasia was treated with deepening trochleoplasty with or without revision MPFL-R, and patella fracture according to the nature of the fracture pattern and bone quality. Though generally, outcomes in the revision scenario across all indications were inferior to those post-primary procedure, overall, revision patients demonstrated positive improvements in pain and instability symptoms. Transverse patella fractures treated with debridement and filling with demineralized bone matrix if required with further fixation according to the fracture pattern. CONCLUSION: The most common causes of MPFL failure in literature published to date, in order of decreasing frequency, are: malposition of the femoral tunnel, unaddressed trochlear dysplasia, and patellar fracture. Although surgical techniques of revision MPFL-R to manage these failures were varied, promising outcomes have been reported to date. Larger prospective comparative studies would be useful to clarify optimal surgical management of MPFL-R failure at long-term follow-up. LEVEL OF EVIDENCE: IV.

Treatments and Sequelae of Pediatric Pathologic Proximal Femur Fractures Due to Benign Bone Cyst.

BACKGROUND: The proximal femur is a common location for pathologic fractures in children, yet there is little published information regarding this injury. The purpose of this study was to investigate the outcomes of pediatric pathologic proximal femur fractures due to benign bone tumors. METHODS: A retrospective review of patients treated for pathologic proximal femur fractures from 2004 to 2018 was conducted. Inclusion criteria were age below 18 years and pathologic proximal femur fracture secondary to a benign bone tumor. Patients were excluded if they had <1 year of follow-up. Medical charts and serial radiographs were reviewed for fracture classification, underlying pathology, treatment, complications, and time to fracture healing. RESULTS: A total of 14 patients were included. Mean age was 6±3 (3 to 11) years, and mean follow-up was 44±21 (22 to 86) months. Index treatment was spica casting in 9/14 (68%) patients, while 5/14 (32%) were treated with internal fixation. Of the 9 patients initially treated with casting, 22% (2/9) required repeat spica casting at a mean of 0.6 months after index treatment, 67% (6/9) required internal fixation at a mean of 20.3 months after index treatment, and 11% (1/9) did not require revision treatment. Eighty-eight percent (8/9) of patients treated with casting required revision treatment compared with 40% (2/5) of those treated with internal fixation (P=0.05). Nonunion occurred after 1 refracture, malunion with coxa vara occurred in 2 fractures, and the remaining 11/14 (84%) fractures had a union at a mean of 4.9±3.0 months All cases of malunion occurred in patients initially treated nonoperatively. There were 19 distinct complications in 10/14 (71%) patients. The incidence of any revision surgery was 64% (9/14). CONCLUSIONS: In this series, pediatric pathologic proximal femur fractures demonstrated prolonged time to union, high incidence of revision surgery (64%), and substantial complication rate (71%). In children with pathologic proximal femur fractures, treatment with internal fixation is recommended as this series showed a 78% failure rate of initial conservative management. LEVEL OF EVIDENCE: Level IV.

Association of autoimmunity and cancer: An emphasis on proteolytic enzymes.

Cancer and autoimmune diseases are the two devastating conditions that together constitute a leading health problem worldwide. The rising burden of these disorders in the developing world demands a multifaceted approach to address the challenges it poses. Understanding the root causes and specific molecular mechanisms by which the progression of the diseases takes place is need of the hour. A strong inflammatory background and common developmental pathways, such as activation of immune cells, proliferation, increased cell survival and migration which are controlled by growth factors and inflammatory cytokines have been considered as the critical culprits in the progression and complications of these disorders. Enzymes are the potential immune modulators which regulate various inflammatory events and can break the circulating immune complexes via macrophages production. In the current manuscript, we have uncovered the possible role of proteolytic enzymes in the pathogenesis and progression of cancer and autoimmune diseases. In the light of the available scientific literature, we advocate in-depth comprehensive studies which will shed light towards the role of proteolytic enzymes in the modulation of inflammatory responses in cancer and autoimmune diseases together.

Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.

INTRODUCTION: Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury. METHODS: We analyzed data from two separate experiments where swine were subjected to lethal insults.  Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy. RESULTS: VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment. CONCLUSIONS: A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.

The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: A meta-analysis of 11 epidemiological studies.

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a widespread chronic liver disease. It is considered a multifactorial disorder that can progress to liver fibrosis and cause a worldwide public health concern. Coffee consumption may have a protective impact on NAFLD and liver fibrosis. However, the evidence from the previous studies is inconsistent. This meta-analysis summarizes available literature. MATERIALS AND METHODS: This study comprises two meta-analyses. The first meta-analysis summarizes the effect of coffee consumption on NAFLD in those who did or did not drink coffee. The second analysis compares the risk of liver fibrosis development between NAFLD patients who did or did not drink coffee. Pooled risk ratios (RR) and confidence intervals (CI) of observational studies were estimated. RESULTS: Of the total collected 321 articles, 11 met our eligibility criteria to be included in the analysis. The risk of NAFLD among those who drank coffee compared to those who did not was significantly lower with a pooled RR value of 0.77 (95% CI 0.60-0.98). Moreover, we also found a significantly reduced risk of liver fibrosis in those who drink coffee than those who did not drink in the NAFLD patients with the relative risk (RR) of 0.68 (95% CI 0.68-0.79). CONCLUSIONS: Regular coffee consumption is significantly associated with a reduced risk of NAFLD. It is also significantly associated with decreased risk of liver fibrosis development in already diagnosed NAFLD patients. Although coffee consumption may be considered an essential preventive measure for NAFLD, this subject needs further epidemiological studies.

Impact of metformin therapy on health-related quality of life outcomes in tuberculosis patients with diabetes mellitus in India: A prospective study.

OBJECTIVE: To assess the impact of metformin use on health-related quality of life (HRQoL) in tuberculosis (TB) patients who are presented with type 2 diabetes mellitus (T2DM). METHODOLOGY: In this community-based prospective study, TB patients attending Hakeem Abdul Hameed Centenary Hospital, New Delhi (India) and had comorbidity of T2DM between April 2018 and July 2019 were enrolled. Patients were divided into metformin users and metformin non-users on the basis of the presence of metformin in their routine as antidiabetic drug(s). HRQoL was determined using a validated TB-specific tool (Dhingra and Rajpal-12 scale ie, DR-12) consists of symptom and socio-psychological and exercise adaptation domains. The HRQoL scores were compared at pretreatment (1st visit), end of intensive phase (2nd visit) and end of treatment (3rd visit) between the two groups. RESULTS: A total of 120 patients were enrolled, of which 24 were excluded as they did not respond at follow-up visits. Among the metformin users (n = 48) the mean age of patients was 47.56 years and 62.50% was males. Among the metformin non-users (n = 48), the mean age of patients was 49.02 years and 54.10% was males. The baseline characteristics were similar in both groups except for the substance used history (P = .025), literacy level (P = .048) and BMI (P = .028). Metformin users demonstrated significant improvement in symptom scores (2nd visit: P < .001; 3rd visit: P = .001) and socio-psychological and exercise adaptation scores (2nd visit: P < .0001; 3rd visit: P < .0001) as compared with metformin non-users at 2nd visit and 3rd visit. Overall, scores were also found to be significantly improved in metformin users (2nd visit: P < .001; 3rd visit: P = .001). CONCLUSION: Metformin therapy exerted favourable effects on HRQoL in patients with TB and T2DM and can be recommended as an adjuvant antitubercular drug in TB patients with co-morbidity of T2DM, unless contraindicated.

Post-operative pain management modalities employed in clinical trials for adult patients in LMIC; a systematic review.

BACKGROUND: Unrelieved postoperative pain afflicts millions each year in low and middle income countries (LMIC). Despite substantial advances in the study of pain, this area remains neglected. Current systematic review was designed to ascertain the types of clinical trials conducted in LMIC on postoperative pain management modalities over the last decade. METHODS: A comprehensive search was performed in June 2019 on PubMed, Cochrane Library, CINAHL Plus, and Web of Science databases to identify relevant trials on the management of postoperative pain in LMIC. Out of 1450 RCTs, 108 studies were reviewed for quality evidence using structured form of critical appraisal skill program. Total of 51 clinical trials were included after applying inclusion/exclusion criteria. RESULTS: Results are charted according to the type of surgery. Eleven trials on laparoscopic cholecystectomy used multimodal analgesia including some form of regional analgesia. Different analgesic modalities were studied in 4 trials on thoracotomy, but none used multimodal approach. In 11 trials on laparotomy, multimodal analgesia was employed along with the studied modalities. In 2 trials on hysterectomy, preemptive pregabalin or gabapentin were used for reduction in rescue analgesia. In 13 trials on breast surgical procedures and 10 on orthopaedic surgery, multimodal analgesia was used with some form of regional analgesia. CONCLUSION: We found that over the past 10 years, clinical trials for postoperative pain modalities have evolved in LMIC according to the current postoperative pain management guidelines i.e. multi-modal approach with some form of regional analgesia. The current review shows that clinical trials were conducted using multimodal analgesia including but not limited to some form of regional analgesia for postoperative pain in LMIC however this research snapshot (of only three countries) may not exactly reflect the clinical practices in all 47 countries. Post Operative Pain Management Modalities Employed in Clinical Trials for Adult Patients in LMIC; A Systematic Review.