Antibacterial Activity of Manuka Honey Against Azithromycin Resistant Extensively Drug Resistant Salmonella Typhi Clinical Isolates: In-Vitro Study

Typhoid fever is a significant health problem in developing countries like Pakistan. Salmonella Typhi the causative agent of typhoid has developed resistant to almost all recommended antibiotics. Emergence of resistance to third generation cephalosporins has further complicated the situation and such strains are called as extensively drug resistant (XDR) Salmonella Typhi. Currently only available options are azithromycin and cabapenems. Recently few reports of azithromycin resistance have emerged from countries like Pakistan, India, Bangladesh and Nepal. As azithromycin is the only oral option available to treat XDR Typhoid, development of resistance may change treatment strategy altogether from out patient management to hospitalization of every patient. This may increase the burden on already weak health care system of countries like Pakistan. So there is dire need to look for the alternative treatment options. Manuka honey is well known for its therapeutic potential against wide range of bacteria including Salmonella Typhimurium. In this study 3 azithromycin resistant isolates were isolated and identified using disc diffusion, E-test and broth micro dilution methods and antibacterial activity, MIC and MBC of manuka honey was performed by agar well diffusion assay and broth micro dilution assay respectively. Manuka honey manifested significant antibacterial activity against all test isolates with zone of inhibition ranging from 7.3mm to 7.5mm, MIC and MBC values were between 10 to 15% v/v Here, we conclude that Manuka honey possess potent antibacterial activity and might be used as an alternative treatment option against azithromycin resistant XDR Typhid. However, further clinical trials are mandatory to validate our initial findings.

Lateral tarsal strip through osteotomies for recurrent ectropion and eyelid laxity correction

Objective to present a surgical technique for treating patients with recurrent ectropion and severe lower eyelid laxity. Methods Lateral tarsal strip and canthal fixation by osteotomy was performed in 6 patients with recurrent ectropion and 1 patient with extreme lower eyelid laxity secondary to an anophthalmic socket. Preoperative and postoperative photographs were evaluated in order to assess the outcomes of the procedure. Patients were followed up 4 weeks, 6 months, 12 months and 24 months of the postoperative period. The initial symptoms of the patients were eye redness, epiphora, foreign body sensation, aesthetic complaints, and facial asymmetry. Symptoms and aesthetic results were assessed by questioning, photographs, and fluorescein and lissamine green stains taken in each visit. Results No postoperative complications were observed. No recurrence episodes were reported during the follow-up period and physical appearance improvement and symptom severity reduction were maintained during the observation. Conclusion Lateral tarsal strip through osteotomies is an effective surgical procedure for treating severe recurrent ectropion cases or lower eyelid laxity and could be considered as an alternative treatment option or even a primary surgical technique in selected difficult cases.

APTC-EC-2A: A Lytic Phage Targeting Multidrug Resistant E. coli Planktonic Cells and Biofilms

Escherichia coli (E. coli) are common bacteria that colonize the human and animal gastrointestinal tract, where they help maintain a balanced microbiome. However, some E. coli strains are pathogenic and can cause serious infectious diseases and life-threatening complications. Due to the overuse of antibiotics and limited development of novel antibiotics, the emergence of antibiotic-resistant strains has threatened modern medicine, whereby common infections can become lethal. Phage therapy has once again attracted interest in recent years as an alternative treatment option to antibiotics for severe infections with antibiotic-resistant strains. The aim of this study was to isolate and characterize phage against multi-drug resistant E. coli isolated from clinical samples and hospital wastewater. For phage isolation, wastewater samples were collected from The Queen Elizabeth Hospital (Adelaide, SA, Australia) followed by phage enrichment as required. Microbiological assays, electron microscopy and genomic sequencing were carried out to characterize the phage. From the 10 isolated E. coli phages, E. coli phage APTC-EC-2A was the most promising and could lyse 6/7 E. coli clinical isolates. APTC-EC-2A was stable at a broad pH range (3–11) and could lyse the host E. coli at temperatures ranging between 30–50 °C. Furthermore, APTC-EC-2A could kill E. coli in planktonic and biofilm form. Electron microscopy and genomic sequencing indicated the phage to be from the Myoviridae family and of lytic nature. In conclusion, the newly isolated phage APTC-EC-2A has the desired properties that support its potential for development as a therapeutic agent against therapy refractory E. coli infections.

Towards Biohybrid Lung Development—Fibronectin-Coating Bestows Hemocompatibility of Gas Exchange Hollow Fiber Membranes by Improving Flow-Resistant Endothelialization

To provide an alternative treatment option for patients with end-stage lung disease, we aim for biohybrid lung development (BHL) based on hollow fiber membrane (HFM) technology used in extracorporeal membrane oxygenators. For long-term BHL application, complete hemocompatibility of all blood-contacting surfaces is indispensable and can be achieved by their endothelialization. Indeed, albumin/heparin (AH) coated HFM enables initial endothelialization, but as inexplicable cell loss under flow conditions was seen, we assessed an alternative HFM coating using fibronectin (FN). Therefore, endothelial cell (EC) adherence and viability on both coated HFM were analyzed by fluorescence-based staining. Functional leukocyte and thrombocyte adhesion assays were performed to evaluate hemocompatibility, also in comparison to blood plasma coated HFM as a clinically relevant control. To assess monolayer resistance and EC behavior under clinically relevant flow conditions, a mock circulation setup was established, which also facilitates imitation of lung-disease specific blood gas settings. Besides quantification of flow-associated cell loss, endothelial responses towards external stimuli, like flow exposure or TNFα stimulation, were analyzed by qRT-PCR, focusing on inflammation, thrombus formation and extracellular matrix production. Under static conditions, both coated HFM enabled the generation of a viable, confluent, non-inflammatory and anti-thrombogenic monolayer. However, by means of homogenous FN coating, cell retention and physiologic gene regulation towards an improved hemocompatible-and extracellular matrix producing phenotype, was significantly superior compared to the inhomogeneous AH coating. In summary, our adaptable in-house FN coating secures the endothelial requirements for long-term BHL application and may promote monolayer establishment on all other blood contacting surfaces of the BHL (e.g., cannulae).

Microvascular myocutaneous and cutaneous free flap reconstruction in patients with terminal esophagostomy after complicated oncological esophagus resection

Summary Background Persisting anastomotic leakage after oncological esophagectomy is a severe problem associated with high mortality and morbidity. Unfortunately, treatment options with promising results are scarce, especially when conventional operative and endoscopic methods have failed. Due to limitation of oral intake and the need for artificial nutrition, quality of life (QOL) is reduced. Microvascular myocutaneous and cutaneous free flap (MFF) reconstruction could be a promising alternative. Methods This retrospective case series presents 7 patients treated between March 2017 and November 2020 at our surgical department, with persisting postoperative anastomotic leakage without further feasible treatment options. All patients received anastomotic MFF reconstruction; used flaps and important intraoperative factors like microvascular anastomosis were evaluated. Complications and patient contentment was assessed. Results The included 7 male patients had median age of 65.15 years (range: 48–75). MFF function was adequate in 6/7 patients, one flap necrosis was encountered. Whereas 5 patients initially had good results, surgical revision was performed in 1 patient to ensure graft function. Postoperative complications appeared in 6/7 patients. Mean duration of inpatient care was 63 days (range: 24–156). At the time of evaluation, 1 patient has died of his malignant disease. No more additional nutrition was needed in 3/6 patients with adequate graft function. Most patients reported improved QOL after MFF. Conclusion MFF free flap can be an alternative treatment option for patients with terminal esophagostomy after complicated oncological esophagus resection without further treatment options. The renewed ability of oral food intake results in a significant improvement of QOL.

Role of Janus Kinase (JAK) Inhibitor in Autoimmune Ocular Inflammation: A Systematic Review

Purpose. To evaluate the effectiveness of Janus kinase (JAK) inhibitors for the treatment of patients with autoimmune disease and associated inflammatory ocular diseases. Methods. We identified relevant literature by screening the MEDLINE, PubMed, and Cochrane databases for randomized controlled trials, cohort studies, case controls, and case reports. Results. Seven studies, including 11 patients, were included in the final systematic analysis. Of the 11 patients, there were 5 cases of juvenile idiopathic arthritis- (JIA-) associated uveitis, 1 case of rheumatoid arthritis- (RA-) associated keratitis, 1 case of RA-associated scleritis, 1 case of psoriasis-associated conjunctivitis, 2 cases of noninfectious scleritis, and 1 case of uveitis with suspected autoimmune disease. None of these 11 patients responded adequately to conventional treatments, including biological agents; these were all refractory cases and switched to JAK inhibitor therapy. Irrespective of whether they were suffering from uveitis, scleritis, or other types of ocular inflammation, all 11 patients showed an improvement to JAK inhibitors without significant side effects. Different types of JAK inhibitors might be associated with different responses when used to treat ocular inflammation. Conclusions. JAK inhibitors may represent an alternative treatment option for patients with autoimmune ocular inflammation.

Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases

Background: Achilles tendinopathy, seen in athletes and manual labor workers, is an inflammatory condition characterized by chronic tendon pain. Owing to the toxicity that develops in various organs attributed to the use of anti–inflammatory drugs, there is a need for new therapeutic agents. Purpose: In the present study, the effects of quercetin (Que), the one that attracted the most attention of researchers studying this group of flavonoids, were investigated against collagenase–induced tendinopathy. Study Design: Controlled laboratory study. Methods: A total of 35 Sprague-Dawley rats were used in the study. Tendinopathy was created by injecting a single dose of collagenase (10 μL; 10 mg/mL) into the tendons of rats. Thirty minutes after the injection, Que was administered at doses of 25 or 50 mg/kg. Que administration was carried out for 7 days. Animals underwent a motility test at the end of the study. In addition, markers of oxidative stress, inflammation, apoptosis, and autophagy, as well as the expression levels of matrix metalloproteinases (MMPs 2, 3, 9, and 13), ICAM-1, and STAT3, were measured in tendon tissues with biochemical, molecular, and Western blot techniques. Results: The results showed that oxidative stress, inflammation, apoptosis, and autophagy were triggered by the injection of collagenase. In addition, MMPs, ICAM-1, and STAT3 were activated to participate in the development of tendinopathy. Que was found to reduce ICAM-1 levels in tendon tissue. Moreover, Que showed antioxidant, anti–inflammatory, antiapoptotic, and antiautophagic effects on tendons against tendinopathy. More important, Que suppressed the expression of MMPs in the tendon tissues. Conclusion: Que has protective properties against collagenase–induced tendon damage in rats. Clinical Relevance: We believe that with further study, Que may be shown to be an alternative treatment option for athletes or others who experience tendon injuries.

Impact of Complete Pulmonary Metastasectomy on the Prognosis of Children with Metastatic Hepatoblastoma: A Single Center Experience

Background The survival rate of patients with hepatoblastoma (HB) with distant metastases is unsatisfactory. Although dose-dense chemotherapy with a high incidence of ototoxicity improves the prognosis of these patients, surgical metastasectomy may provide an alternative treatment option avoiding drug side effects. The aim of this study was to examine the efficacy of “complete” pulmonary metastasectomy for the treatment of children with metastatic HB. Methods This retrospective study retrieved data from 2004 to 2015 on 22 children with metastatic HB. Separated into two groups; children who underwent only hepatectomy (group H, 14 cases), and children who underwent primary or rescue liver transplantation (group T, eight cases). Each patient was administered initial chemotherapy according to JPLT-2, SIOPEL3 or PLADO protocols. Over the course of this study, we performed metastasectomies for all detectable pulmonary metastases. Indocyanine green fluorescent navigation was used for 15 patients to detect tiny metastases. The follow-up period for survivors after the last metastasectomy ranged from 36 to 186 months. Results The cumulative disease-free 5-year survival rate was 84% in group H and 33% in group T. The median number of resected pulmonary metastatic lesions was 10.5 (range: 1-42) in group H and 3.5 (range: 1–97) in group T. None of the survivors developed hearing or respiratory impairment. Conclusions Complete pulmonary metastasectomy improves the prognosis of patients with metastatic HB with conventional chemotherapy, especially in the patients with primary HB lesions removed without liver transplantation.

Hybrid Repair with Reversed Sequence Supra-aortic Debranching in Ruptured Arch Aneurysm

Aortic arch pathology in a high-risk patient in whom the resternotomy approach is unfeasible due to treated mediastinitis after ascending aortic replacement presents a unique challenge for hybrid arch repair (HAR) because of the need for supra-aortic debranching from unusual inflow sites other than the ascending aorta. This report describes a “reversed sequence” extra-anatomical supra-aortic debranching procedure as a salvage technique performed to enable HAR. An 83-year-old woman with a history of ascending aortic replacement for type A aortic dissection, mediastinitis complicated by sternal osteomyelitis, and a chest wall reconstructed with a rectus abdominis myocutaneous flap presented with chest pain because of a contained dissecting arch aneurysm rupture. The patient underwent supra-aortic debranching from the bilateral common femoral arteries and thoracic endovascular aortic repair to the ascending aorta under cerebral near-infrared spectroscopy (NIRS) monitoring. Completion imaging by angiography demonstrated successful exclusion of the ruptured aneurysm. The regional cerebral oxygen saturation level, monitored by NIRS, did not change markedly during surgery. The patient was neurologically intact with adequate cerebral blood flow assessed postoperatively by 123I-IMP single photon emission computed tomography. Total debranching of the supra-aortic vessels from the common femoral artery for inflow is feasible and provides adequate cerebral perfusion. This procedure may offer an alternative treatment option in patients with complex conditions involving aortic arch pathology.