Leveraging access to technology and enhanced surgical technique (LATEST) in laparoscopic bile duct exploration (LBDE).

Single-stage management of choledocholithiasis with concomitant gallstones consists of performing either laparoscopic bile duct exploration (LBDE) or intra-operative endoscopic retrograde cholangiopancreatography at the same time as laparoscopic cholecystectomy. Transductal LBDE is associated with significantly higher post-operative morbidity, longer operative times and longer hospital stay when compared to transcystic LBDE. The aim of this study was to report the transcystic exploration rate and post-operative outcomes from LBDE before and after implementation of the LATEST (Leveraging Access to Technology and Enhanced Surgical Technique) principles. METHODS: A retrospective review of 481 consecutive patients between February 1998 and July 2021 was performed. Patients were assigned into two groups determined by whether they were operated before or after the implementation of LATEST. Data collected included pre-operative demographic information, medical co-morbidity, pre-operative investigations, and intra-operative findings (including transcystic exploration rate, negative choledochoscopy rate, use of holmium laser lithotripsy and operative time). Outcomes of this study were the transcystic exploration rate, stone clearance rate, conversion to open surgery, post-operative morbidity and mortality, and length of post-operative hospital stay. RESULTS: The pre-LATEST group contained 237 patients and the LATEST group comprised of 244 patients. Ultra-thin choledochoscopes and holmium laser lithotripsy were used more frequently in the LATEST group (41.4% and 18.4%, respectively). Enhanced surgical techniques (correction of the cystic duct-CBD junction and the trans-infundibular approach) were also performed more frequently in the LATEST group. More patients in the LATEST group received transcystic LBDE (86.1% vs 11.0%, p < 0.0001). The LATEST group had significantly higher stone clearance rates (98.8% vs 93.7%, p = 0.0034), reduced post-operative morbidity and shorter post-operative hospital stay (4 days vs 1 day, p < 0.0001). CONCLUSIONS: LATEST describes four key factors that can be used when performing LBDE. The adoption of LATEST in LBDE is associated with an increased stone clearance, a higher transcystic exploration rate and reduced post-operative morbidity.

Differences and diversity of autoimmune encephalitis in 77 cases from a single tertiary care center.

BACKGROUND: The incidence of autoimmune encephalitis has risen globally. There are two general categories of disease-associated antibodies that can be tested for: neuronal surface and intracellular. However, testing both groups of autoantibodies are costly. This study aims to identify differences between groups by comparing clinical presentations, radiological findings and CSF profile of patients, and determine if any parameters are indicative of one group of autoantibodies over another. Additionally, we aim to report the local incidence of less common groups of disease-associated antibodies as well. METHODS: Seventy-seven records of autoimmune encephalitis/encephalomyelitis patients admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between October 2010 and February 2017 were reviewed. Patients with infections or those with classic central nervous system demyelinating features were excluded. RESULTS: Of 77 patients, 40% presented with neuronal surface antibodies and 33% had intracellular antibodies. The most common autoantibody detected in each group was anti-NMDAr antibody (25/31, 81%) and anti-Ri antibody (7/25, 28%) respectively. In the neuronal surface antibody group, behavioral change was the most common complaint (45%), followed by seizures (39%) and abnormal movements (29%). In the latter group, seizure was the most common presenting symptom (32%), followed by motor weakness (20%), behavioural change (16%) and abnormal movements (16%). Patients with neuronal surface antibodies were younger (35 vs 48 years old, p = 0.04) and more likely to present with behavioral change (45% vs 16%, p = 0.02). Mortality rate was higher in the intracellular group (16% vs 3.2%, p = 0.09). No differences were detected in magnetic resonance imaging (MRI) and CSF profile. CONCLUSIONS: In the early stages of the disease, both groups have comparable clinical outcomes. Although there were significant differences in age and percentage of patients with behavioral change, both groups of autoimmune encephalitis still shared many clinical features and could not be distinguished based on MRI and CSF profiles. Therefore, we recommend that patients with features of autoimmune encephalitis should be screened for both the neuronal surface and intracellular antibodies regardless of clinical presentation.

CORRELATIONS BETWEEN EXPERIMENTAL MYOPIA MODELS AND HUMAN PATHOLOGIC MYOPIA.

PURPOSE: To analyze the hallmark features of pathologic myopia developed in animal models and compare them with those seen in patients. METHODS: A literature review was performed to identify animal models that exhibited key features of pathologic myopia, namely posterior staphyloma, myopic maculopathy, lacquer cracks, and choroidal neovascularization, either spontaneously or induced by monocular deprivation. Using imaging modalities, such as optical coherence tomography, confocal scanning laser ophthalmoscopy, fluorescein angiography, and electron microscopy, these features were compared with those found in myopic maculopathy of patients. RESULTS: Three types of animals were identified. The LRP2 knockout mice exhibited posterior staphylomas and chorioretinal atrophy at 21 and 60 days after birth, respectively. Retinopathy globe enlarged (rge) chicks and normal lid-sutured chicks developed lacquer cracks and chorioretinal atrophy. Lacquer cracks detected in rge chicks subsequently progressed to patchy chorioretinal atrophy, which is also commonly seen in patients with pathologic myopia. CONCLUSION: The LRP2 knockout mice, retinopathy globe enlarged (rge) chicks, and normal lid-sutured chicks exhibit features typical for myopic maculopathy in patients and could serve to further elucidate the pathogenesis of myopic maculopathy.

Perioperative group and save testing are not routinely indicated for emergency laparoscopic appendicectomy and laparoscopic hernia repairs: A North West London retrospective study.

INTRODUCTION: Two valid group and saves are commonly required for patients undergoing laparoscopic appendicectomy and laparoscopic hernia repairs preoperatively; however, perioperative blood transfusions are seldom required. This is financially burdensome and frequently leads to delays in theatre lists. We performed a retrospective analysis to investigate blood transfusions performed perioperatively and within 28 days of these procedures. METHOD: We used our electronic records to collect data of all laparoscopic appendectomies and laparoscopic hernia repairs between March 2017 and March 2021. Patients of any age undergoing these operations were included. Patients requiring concomitant intra-abdominal surgery or who had incomplete medical records were excluded. RESULTS: A total of 1891 patients were included, of which 1462 (77.3%) had a laparoscopic appendicectomy versus 429 (22.7%) who had a laparoscopic hernia repair. In all, 3507 group and saves were taken costing £47,398.50. One patient (0.068%) required emergency blood transfusion (4 units of red cells) secondary to major haemorrhage. CONCLUSION: Our findings demonstrate that the incidence of perioperative blood transfusions for laparoscopic appendicectomy and laparoscopic hernia repairs is low, challenging the indication for routine preoperative group and saves.

Patient Stratification in Sepsis: Using Metabolomics to Detect Clinical Phenotypes, Sub-Phenotypes and Therapeutic Response.

Infections are common and need minimal treatment; however, occasionally, due to inappropriate immune response, they can develop into a life-threatening condition known as sepsis. Sepsis is a global concern with high morbidity and mortality. There has been little advancement in the treatment of sepsis, outside of antibiotics and supportive measures. Some of the difficulty in identifying novel therapies is the heterogeneity of the condition. Metabolic phenotyping has great potential for gaining understanding of this heterogeneity and how the metabolic fingerprints of patients with sepsis differ based on survival, organ dysfunction, disease severity, type of infection, treatment or causative organism. Moreover, metabolomics offers potential for patient stratification as metabolic profiles obtained from analytical platforms can reflect human individuality and phenotypic variation. This article reviews the most relevant metabolomic studies in sepsis and aims to provide an overview of the metabolic derangements in sepsis and how metabolic phenotyping has been used to identify sub-groups of patients with this condition. Finally, we consider the new avenues that metabolomics could open, exploring novel phenotypes and untangling the heterogeneity of sepsis, by looking at advances made in the field with other -omics technologies.

Inflammatory myopathy occurring shortly after severe acute respiratory syndrome coronavirus 2 vaccination: two case reports.

BACKGROUND: Vaccination remains the cornerstone approach to exiting the current global coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2. The novel messenger ribonucleic acid vaccines offer a high level of protection and are widely used throughout the world. With more people receiving the vaccines, better understanding of their relative safety can be reached. In this report, we describe two patients who developed inflammatory myopathy within 48 hours of receiving the Pfizer BNT162b2 vaccine. CASE PRESENTATION: Patient A, a 55-year-old South East Asian woman, presented with a 6-week history of pruritic facial and torso rash and a 1-week history of worsening proximal myopathy. Her rash first developed 2 days after receiving the first dose of BNT162b2 vaccine. Patient B, a 72-year-old Caucasian woman, presented with a 2-week history of proximal myopathy a day after receiving the second dose of BNT162b2 vaccine. Both patients had elevated creatine kinase on admission. Patient A tested positive for anti-Mi-2a antibody and anti-Ro-52 antibody, while Patient B was positive for anti-fibrillarin antibody. Magnetic resonance imaging subsequently confirmed generalized acute muscle inflammation and subcutaneous inflammation consistent with inflammatory myositis. Both patients did not have a previous history or family history of autoimmune disease. Patients A and B were diagnosed with dermatomyositis and inflammatory myositis, respectively. They were initially treated with pulsed intravenous methylprednisolone followed by oral prednisolone. However, as their conditions were resistant to corticosteroids, both eventually received and responded well to intravenous immunoglobulin therapy. CONCLUSION: There are previously reported cases of severe acute respiratory syndrome coronavirus 2-induced and other vaccine-related inflammatory myopathies. However, the precise mechanisms are not elucidated. Without more evidence and convincing pathophysiology, it is not possible to conclude that our patients developed inflammatory myopathy because of the vaccine. However, the timing of the disease onset and the lack of previous history raise an important question of this novel messenger ribonucleic acid therapy.

IMI Pathologic Myopia.

Pathologic myopia is a major cause of visual impairment worldwide. Pathologic myopia is distinctly different from high myopia. High myopia is a high degree of myopic refractive error, whereas pathologic myopia is defined by a presence of typical complications in the fundus (posterior staphyloma or myopic maculopathy equal to or more serious than diffuse choroidal atrophy). Pathologic myopia often occurs in eyes with high myopia, however its complications especially posterior staphyloma can also occur in eyes without high myopia. Owing to a recent advance in ocular imaging, an objective and accurate diagnosis of pathologic myopia has become possible. Especially, optical coherence tomography has revealed novel lesions like dome-shaped macula and myopic traction maculopathy. Wide-field optical coherence tomography has succeeded in visualizing the entire extent of large staphylomas. The effectiveness of new therapies for complications have been shown, such as anti-VEGF therapies for myopic macular neovascularization and vitreoretinal surgery for myopic traction maculopathy. Myopia, especially childhood myopia, has been increasing rapidly in the world. In parallel with an increase in myopia, the prevalence of high myopia has also been increasing. However, it remains unclear whether or not pathologic myopia will increase in parallel with an increase of myopia itself. In addition, it has remained unclear whether genes responsible for pathologic myopia are the same as those for myopia in general, or whether pathologic myopia is genetically different from other myopia.

Current and emerging pharmaceutical interventions for myopia.

Myopia is a major cause of visual impairment. Its prevalence is growing steadily, especially in East Asia. Despite the immense disease and economic burden, there are currently no Food and Drug Administration-approved drugs for myopia. This review aims to summarise pharmaceutical interventions of myopia at clinical and preclinical stages in the last decade and discuss challenges for preclinical myopia drugs to progress to clinical trials. Atropine and oral 7-methylxanthine are shown to reduce myopia progression in human studies. The former has been extensively studied and is arguably the most successful medication. However, it has side effects and trials on low-dose atropine are ongoing. Other pharmaceutical agents being investigated at a clinical trial level include ketorolac tromethamine, oral riboflavin and BHVI2 (an experimental drug). Since the pathophysiology of myopia is not fully elucidated, numerous drugs have been tested at the preclinical stage and can be broadly categorised based on the proposed mechanisms of myopisation, namely antimuscarinic, dopaminergic, anti-inflammatory and more. However, several agents were injected intravitreally or subconjunctivally, hindering their progress to human trials. Furthermore, with atropine being the most successful medication available, future preclinical interventions should be studied in combination with atropine to optimise the treatment of myopia.

Correction: Ruxolitinib sensitizes ovarian cancer to reduced dose Taxol, limits tumor growth and improves survival in immune competent mice.

[This corrects the article DOI: 10.18632/oncotarget.21541.].

Ruxolitinib sensitizes ovarian cancer to reduced dose Taxol, limits tumor growth and improves survival in immune competent mice.

Background: Chemotherapy initially reduces the tumor burden in patients with ovarian cancer. However, tumors recur in over 70% of patients, creating the need for novel therapeutic approaches. Methods: We evaluated Ruxolitinib, an FDA-approved JAK 1/2 kinase inhibitor, as a potential adjunctive therapy for use with low-dose Taxol (Paclitaxel) by assessing the impact on in vitro proliferation and colony formation of ID8 cells or human TOV-112D ovarian cancer cells, as well as flow cytometric measurement of surface markers associated with cellular stress and stemness by ID8 cells. The syngeneic ID8 murine model of ovarian cancer was used to assess the impact of Ruxolitinib and Taxol, individually and in combination, on tumor initiation and growth, as well as capacity to extend survival. Results: Ruxolitinib (≤10 µM) sensitized both ID8 and TOV-112D cells to low concentrations of Taxol (≤5 nM), limiting cell proliferation and colony formation in vitro. Mechanistically, we demonstrated that Taxol induced expression of stress and stemness markers including GRP78 and CD133 was significantly reduced by addition of Ruxolitinib. Finally, we demonstrated that a single administration of a low-dose of Taxol (10 mg/Kg) together with daily Ruxolitinib (30 mg/Kg; which is equivalent to plasma concentrations of ∼ 0.01 µM steady-state) limited ID8 tumor growth in vivo and significantly extended median survival up to 53.5% (median 70 v 107.5 days) as compared to control mice. Conclusion: Together, these data support the use of Ruxolitinib in combination with low-dose Taxol as a therapeutic approach with the potential for improved efficacy and reduced side effects for patients with recurrent ovarian cancer.