Five Times Reactivation of COVID-19 in a Patient with Thymoma.

BACKGROUND: The possibility of recurrence in COVID-19 is very rare and hence mostly underdiagnosed. In the face of pandemic, this can lead to circulation of the virus like a hidden iceberg. Better understanding about this topic can improve our knowledge of the COVID-19 pathogenesis and ways to control the transmission. CASE PRESENTATION: A 41 year old male with no known comorbidities was admitted five times during a period of 7 months each time after being detected RTPCR positive for SARS-CoV-2 and more symptomatic than previously. He had no contact with other COVID-19 patients and was asymptomatic in between admissions. Despite this, he did not develop antibodies against SARSCoV-2. Later on, he was diagnosed with thymoma on biopsy of the anterior mediastinal mass. Patient's condition deteriorated on last hospitalization and he died, despite the treatment. Here we present an interesting report on multiple times recurrent COVID-19 infection, probably a case of reactivation and different plausible explanations on the role of thymoma.;Conclusion: Acknowledging the potential of SARS-CoV-2 to cause recurrence is very important during the pandemic as a part of the long term transmission mitigation. The case report shows that previous infection does not guarantee complete immunity from COVID-19, especially in immuno-compromised patients. Hence, despite the status of prior infection, vulnerable individuals who recovered from COVID-19 should be under surveillance.

Comparison of post-operative pain scores and opioid use between kyphoplasty and radiofrequency ablation (RFA) systems combined with cement augmentation.

OBJECTIVE: This retrospective chart review study aims to compare demographic information, post-operative pain scores, and opioid use following treatment with kyphoplasty alone, OsteoCool™ (Medtronic) system, and SpineSTAR ® (Merit Medicine). MATERIALS AND METHODS: Following institutional review board approval, retrospective chart review of 64 patients was examined between January 2011 and December 2017. Inclusion criteria for this study comprised patients greater than 18 years old having metastatic vertebral compression fracture involving the thoracolumbar spine. Exclusion criteria consisted of non-pathologic osteoporotic compression fractures, metastasis in cervical spine, or previous radiofrequency ablation (RFA) treatment. Age at intervention, gender, previous treatment, and nursing recorded VAS score from 0 to 10, with zero representing no pain and 10 representing worst pain were compared. Pain scores documented immediately pre- and post-operatively, as well as 7-14 days post-operatively were targeted for analysis. Post-procedure opioid intake during the first month following surgery was also assessed. RESULTS: A total of 63 patients were included in this retrospective analysis. The demographic characteristics between the treatment arms were similar. Difference of square means analysis showed no statistical difference in pain scores at each time interval between the two RFA systems, or was there a statistical difference in pain scores when each RFA system was compared independently to kyphoplasty alone. Chi-squared analysis showed no statistical difference in opioid use between the treatment arms 1 month post-operatively. DISCUSSION: To our knowledge, this is the first study that evaluates post-operative pain scores between the two novel RFA systems and kyphoplasty alone. Each system results in improved pain scores post-operatively; however, no additional benefit was seen from the addition of RFA.

Role of anti-oxidant (vitamin-C) in post-operative pain relief in foot and ankle trauma surgery: A prospective randomized trial.

BACKGROUND: Post-operative pain may adversely affect a patient's quality of life. Studies have shown that vitamin C, being an anti-oxidant and neuro-modulating agent, can help to reduce pain in a variety of clinical settings. The objective of this randomized controlled trial was to assess the effectiveness of vitamin C in reducing post-operative pain, analgesia requirements and improving functional outcome. METHODS: Patients with isolated foot and ankle trauma, who had undergone surgery, were randomly assigned to receive either vitamin C 500mg or a placebo tablet twice a day. VAS score, analgesia requirement and functional outcome were assessed during their regular follow up. Results were compared and analyzed at the end of 3 months. RESULTS: The group which received vitamin C, showed improvement in VAS score at the end of second and sixth week of follow up, reduced analgesia requirements and improved functional outcome as compared to the placebo group. CONCLUSIONS: This study shows that the supplementation of vitamin C in patients undergoing surgery for foot and ankle trauma helps to reduce analgesic requirements, improve VAS scores and achieve better functional outcome.

Analysis of risk factors for failure of arthroscopic ankle fusion in a series of 52 ankles.

BACKGROUND: The purpose of this retrospective study is to analyze the effect of different variables on union rate and functional outcome in patients who underwent arthroscopic ankle fusion for end-stage arthritis of ankle. METHODS: Clinical records and radiographs were reviewed to evaluate the variables that could predispose patients to non-union and poor functional outcome. Union and functional outcomes were correlated with different variables. RESULTS: Fifty patients had arthroscopic ankle fusion on 52 ankles. The mean age at the time of surgery was 59.4 (27-80) years and mean length of follow up was 32.1 (8-78) months. Forty-eight out of 52 ankles (92.3%) achieved radiographic and clinical union. The average time to fusion was 12.2 (8-28) weeks. The time taken for union was significantly higher in smokers as compared to non-smokers (p<0.001). All the patients in this series who had non-union shared one common factor - neuromuscular imbalance. Age, gender, smoking, diabetes, steroid, bisphosphonates, neuropathy, frontal and sagittal plane alignment and tibial-axis-to-talus (T:T) ratio did not significantly affect the union rate and functional outcome. CONCLUSION: Smokers should refrain from smoking before surgery and patients with neuromuscular problems may require more rigid fixation and a longer period of immobilization to achieve more consistent union rates.

Pregnane X Receptor and P-glycoprotein: a connexion for Alzheimer's disease management.

The translational failure between preclinical animal models and clinical outcome has alarmed us to search for a new strategy in the treatment of Alzheimer's disease (AD). Interlink between Pregnane X Receptor (PXR) and P-glycoprotein (Pgp) at the blood brain barrier (BBB) has raised hope toward a new disease modifying therapy in AD. Pgp is a major efflux transporter for beta amyloid (Aß) at human BBB. A literature survey reveals diminished expression of Pgp transporter at the BBB in AD patients. Pregnane X Receptor is a major transcriptional regulator of Pgp. Restoration of Pgp at the BBB enhances the elimination of the Aß from brain alongside and inhibits the apical to basolateral movement of Aß from the circulatory blood. This review concentrates on in vitro, in vivo, and in silico advancements on the study of the PXR in context to Pgp and discusses the substrate and inhibitor specificity between PXR and Pgp.

Ligamentous advancement for the treatment of subacute syndesmotic injuries. Report of a new technique in 5 cases.

BACKGROUND: Integrity and optimum functioning of the syndesmotic ligament complex is of paramount importance for stability of the ankle joint during various ankle movements. Persistent widening and chronic isolated instability of the distal tibio-fibular syndesmosis leads to poor functional outcome and the development of osteoarthritis. In subacute total ruptures the focus of treatment is to restore the normal anatomy by repair of the ruptured ligament and to protect the reconstruction for a period of time. Various techniques have been previously reported with good results but associated with donor site morbidity and multiple incisions. METHOD: Ligamentous advancement allows repair of the syndesmosis when the AITFL is dysfunctional but intact. The lax AITFL was mobilised with periosteum from the tibia leaving the fibular side intact. The Syndesmosis was cleared, reduced with a clamp, and held with two syndesmotic screws inserted transversely between the distal fibular and tibial shafts. The tibial surface was roughened to receive the new attachment of AITFL. The sleeve of tissue was then secured to the roughened tibial surface under tension using suture anchors with the ankle in neutral position. The repair was protected with a two hole plate and screws. RESULTS: The functional outcome scores showed excellent outcome at the end of 6 months. CONCLUSION: Ligamentous advancement technique obviates the need of any bony procedure and does not involve the use of any material which will lead to any sort of foreign body reaction or donor site morbidity while providing anatomical reconstruction of the syndesmosis with excellent functional outcome.

Human cord blood-derived multipotent stem cells (CB-SCs) treated with all-trans-retinoic acid (ATRA) give rise to dopamine neurons.

Parkinson's disease (PD) results from the chronic degeneration of dopaminergic neurons. A replacement for these neurons has the potential to provide a clinical cure and/or lasting treatment for symptoms of the disease. Human cord blood-derived multipotent stem cells (CB-SCs) display embryonic stem cell characteristics, including multi-potential differentiation. To explore their therapeutic potential in PD, we examined whether CB-SCs could be induced to differentiate into dopamine neurons in the presence of all-trans retinoic acid (ATRA). Prior to treatment, CB-SCs expressed mRNA and protein for the key dopaminergic transcription factors Nurr1, Wnt1, and En1. Following treatment with 10 µM ATRA for 12 days, CB-SCs displayed elongated neuronal-like morphologies. Immunocytochemistry revealed that 48 ± 11% of ATRA-treated cells were positive for tyrosine hydroxylase (TH), and 36 ± 9% of cells were positive for dopamine transporter (DAT). In contrast, control CB-SCs (culture medium only) expressed only background levels of TH and DAT. Finally, ATRA-treated CB-SCs challenged with potassium released increased levels of dopamine compared to control. These data demonstrate that ATRA induces differentiation of CB-SCs into dopaminergic neurons. This finding may lead to the development of an alternative approach to stem cell therapy for Parkinson's disease.

Auto-acetylation stabilizes p300 in cardiac myocytes during acute oxidative stress, promoting STAT3 accumulation and cell survival.

The nuclear acetyltransferase p300 is rapidly and stably induced in the heart during hemodynamic stress, but the mechanism of this induction is unknown. To determine the role of oxidative stress in p300 induction, we exposed neonatal rat cardiac myocytes to doxorubicin (DOX, 1 µM) or its vehicle, and monitored p300 protein content and stability for 24 h. Levels of p300 rose substantially within 1 h and remained elevated for at least 24 h, while p300 transcript levels declined. In the presence of cycloheximide, the estimated half-life of p300 in control cells was approximately 4.5 h, typical of an immediate-early response protein. DOX treatment prolonged p300 t(1/2) to >24 h, indicating that the sharp rise in p300 levels was attributable to rapid protein stabilization. p300 stabilization was entirely due to an increase in acetylated p300 species with greatly enhanced resistance to proteasomal degradation. The half-life of p300 was dependent on its acetyltransferase activity, falling in the presence of p300 inhibitors curcumin and anacardic acid, and increasing with histone deacetylase (HDAC) inhibition. At the same time, acetyl-STAT3, phospho-STAT3-(Tyr 705) and -(Ser 727) increased, together with a prolongation of STAT3 half-life. SiRNA-mediated p300 knockdown abrogated all of these effects, and strongly enhanced DOX-mediated myocyte apoptosis. We conclude that DOX induces an acute amplification of p300 levels through auto-acetylation and stabilization. In turn, elevated p300 provides a key defense against acute oxidative stress in cardiac myocytes by acetylation, activation, and stabilization of STAT3. Our results suggest that HDAC inhibitors could potentially reduce acute anthracycline-mediated cardiotoxicity by promoting p300 auto-acetylation.

Efficacy of intra-articular tranexamic acid in blood loss reduction following primary unilateral total knee arthroplasty.

PURPOSE: The surgical stress of total knee arthroplasty (TKA) procedure and the application of intra-operative pneumatic thigh tourniquet increases local fibrinolytic activity, which contributes significantly to post-operative blood loss. Tranexamic acid, an antifibrinolytic drug, is commonly used to control post-operative blood loss. The recommended mode of administration of tranexamic acid is either oral or intravenous. However, the mechanism of action of the tranexamic acid points towards the possible effectiveness it may have following local/intra-articular application. This prospective, double-blinded, randomized preliminary study evaluated the efficacy of intra-articular tranexamic acid in reducing TKA-associated post-operative blood loss. METHODS: Fifty consenting patients with osteoarthritis of the knee scheduled for primary unilateral cemented-TKA were randomly allocated to one of the two groups: Tranexamic Acid (TA) group (n = 25, 500 mg/5 ml tranexamic acid) and the control group (n = 25, 5 ml 0.9% saline). The drug and control solution were administered intra-articularly through the drain tube immediately after the wound closure. Parameters related to blood loss (drop in haemoglobin, haematocrit differential) and the drain output [volume (ml)] were compared between the two groups. RESULTS: On a comparative basis, TA-group obtained significant reduction in the drain output [95% CI: 360.41-539.59, p < 0.001] at 48 h post-operatively. Even though the control group received sixfold more blood transfusion than TA-group, it showed a greater drop in haemoglobin and haematocrit (p < 0.05). CONCLUSIONS: Local application of tranexamic acid seems to be effective in reducing post-TKA blood loss as well as blood transfusion requirements. LEVEL OF EVIDENCE: Therapeutic study, Level II.

Extensive Giant Tuberous and Tendon Xanthomas in a 48-year-old Gentleman: A Case Report.

INTRODUCTION: Xanthomas are defined as benign lesions characterized by an accumulation of lipid-laden macrophages that develop in the cutis and subcutaneous tissue. Xanthomas are classified as eruptive, tuberous, tendinous, or planar depending on their location and clinical appearance. Co-existence of both tuberous and tendinous forms in an atypical large-sized pattern is a rarity and presented herewith. CASE PRESENTATION: A 48-year-old male patient presented with multiple large masses in his elbows, knees, Achilles tendons, feet, and hands. The largest swellings measured 12 cm × 10 cm in dimensions. The blood workup of the patient showed an elevated level of low-density lipoprotein cholesterol and was subsequently diagnosed with Type IIa familial hypercholesterolemia and multiple large co-existing tuberous and tendinous xanthomas which is a rare clinical presentation. Local surgical excision was performed to remove the symptomatic massive xanthomas from the elbows, knees, and feet. Histological analysis of the surgical specimens confirmed the clinical diagnosis of xanthomas. CONCLUSION: Tuberous and tendinous xanthomas can co-exist in the same patient, including atypical large-sized forms. Usually, patients with xanthomas have some underlying metabolic lipid derangement and a cardiology workup to detect future cardiac risk is warranted. Intervention at an early stage can prevent the formation of disfiguring xanthomas in patients with underlying lipid disorder. The case also highlights a multi-disciplinary approach to such rare clinical presentations.

Selective destruction of mouse islet beta cells by human T lymphocytes in a newly-established humanized type 1 diabetic model.

Type 1 diabetes (T1D) is caused by a T cell-mediated autoimmune response that leads to the loss of insulin-producing beta cells. The optimal preclinical testing of promising therapies would be aided by a humanized immune-mediated T1D model. We develop this model in NOD-scid IL2rgamma(null) mice. The selective destruction of pancreatic islet beta cells was mediated by human T lymphocytes after an initial trigger was supplied by the injection of irradiated spleen mononuclear cells (SMC) from diabetic nonobese diabetic (NOD) mice. This resulted in severe insulitis, a marked loss of total beta-cell mass, and other related phenotypes of T1D. The migration of human T cells to pancreatic islets was controlled by the beta cell-produced highly conserved chemokine stromal cell-derived factor 1 (SDF-1) and its receptor C-X-C chemokine receptor (CXCR) 4, as demonstrated by in vivo blocking experiments using antibody to CXCR4. The specificity of humanized T cell-mediated immune responses against islet beta cells was generated by the local inflammatory microenvironment in pancreatic islets including human CD4(+) T cell infiltration and clonal expansion, and the mouse islet beta-cell-derived CD1d-mediated human iNKT activation. The selective destruction of mouse islet beta cells by a human T cell-mediated immune response in this humanized T1D model can mimic those observed in T1D patients. This model can provide a valuable tool for translational research into T1D.

Prognostic Factors in Paranasal Sinus Squamous Cell Carcinoma and Adenocarcinoma: A SEER Database Analysis.

Background Outcome studies on sinonasal malignancy are limited to retrospective case series, often with inclusion of diverse histology and short follow-up. The objective of this study was to identify key predictive variables that independently impact survival for paranasal sinus squamous cell carcinoma (SCC) and adenocarcinoma (AC) and to compare these variables in the context of these two distinct clinicopathologic entities. Methods: Analysis was conducted using the Surveillance, Epidemiology, and End Results database from 1973 to 2012 to identify key variables that impact survival for SCC and AC. Results A total of 3,714 cases were included. There were 2,895 SCC cases and 819 AC cases. The mean age at diagnosis was 64.1 years. The male to female ratio for SCC and AC was 1.85 and 1.04, respectively. Patients with SCC and AC were most often diagnosed with stage IV disease in 61.8 and 63.4% of cases, respectively. The majority of patients received combined surgery and radiation (52% for SCC and 43.1% for AC). For SCC, increased age ( p < 0.001) and stage ( p < 0.001) were negative predictors, and surgery improved survival ( p < 0.001) on multivariate analysis. For AC, prognostic factors associated with worse survival include increased age ( p < 0.001) and grade ( p < 0.001) on multivariate analysis. Overall survival was significantly higher in AC compared with SCC at 5 years ( p = 0.001). Conclusion SCC and AC of the paranasal sinuses are both aggressive malignancies with poor survival. For both histological subtypes, increased age predicts worse survival and grade also closely links to survival in AC. These data have important potential implications for treatment planning and pretreatment counseling.

Comparison of Plantar Fasciitis Injected With Platelet-Rich Plasma vs Corticosteroids.

BACKGROUND: Plantar fasciitis is one of the most common causes of heel pain. This prospective study compared the efficacy of local injection of corticosteroids vs platelet-rich plasma (PRP) in the treatment of plantar fasciitis. METHODS: Patients were randomly allocated into 2 groups of 40 each (group A and group B). Patients were treated with local corticosteroid injection in group A and autologous PRP injection in group B. Clinical assessment was done prior to the injection and at 1 month, 3 months, and 6 months following the injection, which included visual analog pain scale, subjective rating using the modified Roles and Maudsley score, functional outcome score by the Foot and Ankle Outcome Instrument (FAI) core scale, and the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scale. Radiological assessment was done by measuring the thickness of the plantar fascia using ultrasonography. The mean age, sex, and body mass index of both groups were comparable. RESULTS: Postinjection, there was significant improvement of visual analog score, modified Roles and Maudsley score, FAI core scale, AOFAS ankle-hindfoot score, and plantar fascia thickness in both the groups. However, with the numbers available, no significant difference in improvement could be detected between the above-mentioned variables in the 2 groups. CONCLUSION: We found that the treatment of plantar fasciitis with steroid or PRP injection was equally effective. LEVEL OF EVIDENCE: Level II, prospective randomized comparative series.

Obturator Dislocation of Hip with Ipsilateral Fracture Neck Femur-A Case Report.

INTRODUCTION: Traumatic dislocation of the hip with ipsilateral fracture neck femur is a rare injury because of the different mechanism of both these injuries. The management of such injuries is a challenge as the chances of nonunion and avascular necrosis of femoral head are very high with fixation methods. We report a case of obturator dislocation of the hip with ipsilateral fracture neck of the femur which was treated with uncemented total hip replacement. CASE REPORT: A 32-year-old male sustained obturator dislocation with ipsilateral fracture neck femur following road traffic accident. After initial assessment and treatment, definitive treatment was carried out. Hip was approached through Watson-Jones approach. The head and neck was found to be dislocated and lying close to obturator foramen. A button hole through the anterior capsule and medium-sized chondral defect of the femoral head articular surface was noted. An uncemented total hip arthroplasty was performed. Post-operative period was uneventful and the patient was mobilized weight-bearing as tolerated with walker. He was discharged on the 5th post-operative day. He regained pain-free good range of motion over a period of 6 weeks. CONCLUSION: Fracture pattern combining obturator dislocation and ipsilateral fracture neck femur is a rare injury. Although both head preservation and replacement methods of treatment are available, the choice of treatment depends on duration of injury, age of the patient, associated chondral injuries of femoral head, and the patient's choice. The antero-lateral or lateral approach helps to deal with the anteriorly lying head in a better way as compared to the postero-lateral approach.

Reversal of pathological cardiac hypertrophy via the MEF2-coregulator interface.

Cardiac hypertrophy, as a response to hemodynamic stress, is associated with cardiac dysfunction and death, but whether hypertrophy itself represents a pathological process remains unclear. Hypertrophy is driven by changes in myocardial gene expression that require the MEF2 family of DNA-binding transcription factors, as well as the nuclear lysine acetyltransferase p300. Here we used genetic and small-molecule probes to determine the effects of preventing MEF2 acetylation on cardiac adaptation to stress. Both nonacetylatable MEF2 mutants and 8MI, a molecule designed to interfere with MEF2-coregulator binding, prevented hypertrophy in cultured cardiac myocytes. 8MI prevented cardiac hypertrophy in 3 distinct stress models, and reversed established hypertrophy in vivo, associated with normalization of myocardial structure and function. The effects of 8MI were reversible, and did not prevent training effects of swimming. Mechanistically, 8MI blocked stress-induced MEF2 acetylation, nuclear export of class II histone deacetylases HDAC4 and -5, and p300 induction, without impeding HDAC4 phosphorylation. Correspondingly, 8MI transformed the transcriptional response to pressure overload, normalizing almost all 232 genes dysregulated by hemodynamic stress. We conclude that MEF2 acetylation is required for development and maintenance of pathological cardiac hypertrophy, and that blocking MEF2 acetylation can permit recovery from hypertrophy without impairing physiologic adaptation.

Hoffa's fracture - lateral meniscus obstructing the fracture reduction - a case report.

Hoffa's fracture is a coronal fracture of the posterior femoral condyle and is an unusual injury. It can be easily missed on plain radiographs. There is no dearth of literature on Hoffa's fracture, its various presentations, management and rehabilitation principles. The intra-articular nature of the fracture, vulnerable blood supply of the posterior femoral condyle, involvement of the weight bearing articular surface of the knee and the unstable fracture pattern necessitate the surgical management. We encountered an unusual case of Hoffa's fracture where the lateral meniscus was blocking the reduction of fractured fragments. The patient required mini arthrotomy to remove the meniscus from in between the bone fragments. The fracture was fixed with two anteroposterior screws and knee was immobilised in extension. A gentle knee range of movements was commenced after the wound had healed but weight bearing was delayed for 12 weeks.

Electronic transport properties of BN sheet on adsorption of ammonia (NH3) gas.

We report the detection of ammonia gas through electronic and transport properties analysis of boron nitride sheet. The density functional theory (DFT) based ab initio approach has been used to calculate the electronic and transport properties of BN sheet in presence of ammonia gas. Analysis confirms that the band gap of the sheet increases due to presence of ammonia. Out of different positions, the bridge site is the most favorable position for adsorption of ammonia and the mechanism of interaction falls between weak electrostatic interaction and chemisorption. On relaxation, change in the bond angles of the ammonia molecule in various configurations has been reported with the distance between NH3 and the sheet. An increase in the transmission of electrons has been observed on increasing the bias voltage and I-V relationship. This confirms that, the current increases on applying the bias when ammonia is introduced while a very small current flows for pure BN sheet.

Factor X deficiency--a rare disorder.

Congenital factor X deficiency is a very rare inherited coagulation disorder. The clinical phenotype is of varying bleeding manifestations depending upon the level of factor activity. We describe a one and a half year old patient with severe deficiency (factor level less than 1%) who manifested with only easy bruisability and epistaxis that does not correlate with level of deficiency.

Ab-initio study of structural, electronic, and transport properties of zigzag GaP nanotubes.

Stability and electronic properties of zigzag (3 ≤ n ≤ 16) gallium phosphide nanotubes (GaP NTs) have been analyzed by employing a systematic ab-intio approach based on density functional theory using generalized gradient approximation with revised Perdew Burke Ernzerhoff type parameterization. Diameter dependence of bond length, buckling, binding energy, and band gap has been investigated and the analysis shows that the bond length and buckling decreases with increasing diameter of the tube, highest binding energy of (16, 0) confirms this as the most stable amongst all the NTs taken into consideration. The present GaP NTs shows direct band gap and it increases with diameter of the tubes. Using a two probe model for (4, 0) NT the I-V relationship shows an exponential increase in current on applying bias voltage beyond 1.73 volt.

Human pregnane X receptor: a novel target for anticancer drug development.

Multidrug resistance (MDR), a significant barrier to effective pharmacokinetics and pharmacodynamics of anticancer drugs, is mainly due to the induction potential of anticancer drugs for drug metabolizing enzymes (DMEs) and efflux transporters through nuclear receptors. Human Pregnane X Receptor (hPXR) is master transcription factor for cytochrome P450 3A4 (CYP3A4) and multidrug resistance protein 1 (MDR1). The hPXR is capable of being activated by structurally diverse ligands. Several studies, like in silico modeling, in vitro assays, and in vivo experimentation have been conducted to identify the structural features of ligand for activation of hPXR. This review highlights hPXR as an appealing target for both the development of novel anticancer drugs and the improvement in preclinical and clinical evaluation of anticancer drugs.