Acute Renal Thrombotic Microangiopathy Caused by Eltrombopag and Romiplostim in a Patient with Myelodysplastic Syndromes (MDS) and Underlying Antiphospholipid Syndrome.

Romiplostim and eltrombopag are synthetic agonists of the thrombopoietin receptor (TPO-R), commonly used for immune thrombocytopenic purpura (ITP) and sometimes in myelodysplastic syndrome (MDS). They are rarely associated with kidney injury. We report a case of acute kidney injury caused by romiplostim and eltrombopag in an 80-year-old male patient with MDS and ITP. He did not have systemic haemolysis syndrome but isolated acute renal thrombotic microangiopathy confirmed by kidney biopsy. He was treated with steroids, plasmapheresis and anticoagulation, with improvement in renal function. Interestingly, the patient had high antiphospholipid (aPL) antibodies noted upon screening, indicating a possible new antiphospholipid syndrome (APS) diagnosis. In the presence of circulating aPL antibodies, eltrombopag may have served as a trigger, causing endothelial injury and subsequent renal microangiopathy; aPL antibodies were still significantly positive at four weeks of outpatient testing. This case and a few others reported in the literature highlight the importance of screening for aPL antibodies before initiating TPO-R agonists in patients with ITP. We suspect that using TPO-R agonists, rather than underlying aPL, caused renal failure. LEARNING POINTS: Synthetic agonists of the thrombopoietin receptor, such as romiplostim or eltrombopag, can cause acute renal failure.Preexisting antiphospholipid (aPL) antibodies may increase the risk of renal failure.Screening for aPL antibodies should be considered before initiating thrombopoietin-receptor agonists (TPO-R agonists) in patients with immune thrombocytopenic purpura (ITP).

Cutaneous Pneumocystis Jirovecii Infection in an Allogeneic Stem Cell Transplant Recipient.

Pneumocystis jirovecii is an opportunistic fungus that infects the lungs but can involve other organs, including the skin and lymph nodes. Risk factors include human immunodeficiency virus (HIV), solid organ/haematological malignancies and a CD4 cell count of fewer than 200 cells/µl. Pneumocystis jirovecii pneumonia (PJP) infection is reported less frequently these days with the advent of prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). We report a case of extrapulmonary PJP infection in a patient while receiving pentamidine prophylaxis in a T-cell prolymphocytic leukaemia, who underwent an allogeneic stem cell transplant. There are plenty of reported cases of PJP on pentamidine prophylaxis; however, none had cutaneous PJP infection. Cutaneous P. jirovecii infection (CPJ) is an extrapulmonary infection that is rarely reported. Our patient's skin biopsy was inconclusive, but the skin nodules improved once he was initiated on TMP-SMX. Many transplant patients cannot tolerate TMP-SMX for various reasons and are placed on second-line prophylaxis for PJP, which does not prevent extrapulmonary PJP infections. Our case highlights the challenges of diagnosing such a rare infection in immunocompromised patients. Extrapulmonary PJP should be suspected in patients with a history of pulmonary PJP and persistent elevated Fungitell® levels in low CD4 counts. LEARNING POINTS: Extrapulmonary Pneumocystis jirovecii pneumonia (PJP) infection can happen while receiving pentamidine prophylaxis.It is extremely rare to see a cutaneous infection, and no case has been reported in the last two decades.Trimethoprim-sulfamethoxazole (TMP-SMX) remains the first-line treatment for pulmonary and extrapulmonary PJP.

Does Risk Mitigation Reduce 90-Day Complications in Patients Undergoing Total Knee Arthroplasty?: A Cohort Study.

BACKGROUND: With ever-increasing demand for total knee arthroplasty (TKA), most healthcare systems around the world are concerned about its socioeconomic burden. Most centers have universally adopted well-defined clinical care pathways to minimize adverse outcomes, maximize volume, and limit costs. However, there are no prospective comparative trials reporting benefits of these risk mitigation (RM) strategies. METHODS: This is a prospective cohort study comparing post-TKA 90-day complications between patients undergoing RM before surgery and those following a standard protocol (SP). In the RM group, we used a 20-point checklist to screen for modifiable risk factors and evaluate the need for optimizing non-modifiable comorbidities. Only when optimization goals were achieved, patients were offered TKA. RESULTS: TKA was performed in 811 patients in the SP group and in 829 in the RM group, 40% of which were simultaneous bilateral TKA. In both groups, hypertension was the most prevalent comorbidity (48%), followed by diabetes (20%). A total of 43 (5.3%) procedure-related complications were seen over the 90-day postoperative period in the SP group, which was significantly greater than 26 (3.1%) seen in the RM group (p = 0.039). The commonest complication was pulmonary thromboembolic, 6 in each group. Blood transfusion rate was higher in the SP group (6%) than in the RM group (< 1%). CONCLUSIONS: Screening and RM can reduce 90-day complications in patients undergoing TKA.

Clinical profile of patients with hyponatremia in a tertiary care hospital in the sub-Himalayan region.

INTRODUCTION: Hyponatremia, defined as a serum sodium concentration ([Na+]) <135 mEq/L. It is not a disease but rather a pathophysiologic process indicating disturbed water homeostasis. Hyponatremia should be further classified to provide directions for diagnosis and treatment. It is a heterogeneous disorder. The classifications of hyponatremia are commonly based on tonicity and volume status. The initial differentiation in hypotonic and non-hypotonic hyponatremia is important because management is different. Several studies have been conducted previously to measure the incidence of hyponatremia in medically ill patients. Several studies have demonstrated an increased prevalence of hyponatremia in the presence of co-morbid conditions. We conducted this study to bring out various causes of hyponatremia; their relation with sex, age and outcome and hyponatremia's classification and incidence in our hospitalised population. MATERIALS AND METHODS: This study was conducted to find out etiology, classification, prevalence and outcome and its relation with age and sex in patients of hyponatremia admitted in our institution. A total number of 106 patients were studied. RESULTS: Hospital-based incidence of hyponatremia was found to be 1.17%. Mean age of patients in study was 62.25 ± 17.7 years. Male to female ratio was 1.25:1. Altered sensorium was the most common neurological symptom. Ninety-five (90%) patients were hypo-osmolar. Out of ninety four patients, 38 (40%) were euvolemic. Chronic obstructive pulmonary disorder (COPD) with cor pulmonale with right-sided heart failure (n = 9, 31%) was the most common cause in hyper-volemic hyponatremia. Acute gastroenteritis (n = 13, 48%) was the most common cause in hypo-volemic hyponatremia. Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was the most common cause (n = 20, 53%) of euvolemic hyponatremia. Out of 106 patients, 11 (10.38%) patients expired. CONCLUSION: Hyponatremia acts as a poor prognostic marker of the primary disease. It is important to recognise it early because of the potential morbidity and mortality, economic impact on the patients and health care associated with it. Early management of hyponatremia, which includes determination of the rate of correction, the appropriate interventions and the presence of other underlying disorders, may help in improving the outcome and shortening the hospital stay of the patients.

Validation of acute exacerbation of chronic obstructive pulmonary disease (COPD) recording in electronic health records: a systematic review protocol.

INTRODUCTION: Many patients with chronic obstructive pulmonary disease (COPD) experience a sustained worsening in symptoms termed an acute exacerbation (AECOPD). AECOPDs impact on patients' quality of life and lung function, are costly to health services and are an important topic for research. Electronic health records (EHR) are increasingly being used to study AECOPD, requiring accurate detection of AECOPD in EHRs to ensure generalisable results. The aim of this protocol is to provide an overview of studies that validate AECOPD definitions used in EHRs and administrative claims databases. METHODS AND ANALYSIS: Medline and Embase will be searched for terms related to COPD exacerbation, EHRs and validation. All studies published between 1 January 1990 and 30 September 2019 written in English that validate AECOPD in EHRs and administrative claims databases will be considered. INCLUSION CRITERIA: EHR data must be routinely collected; the AECOPD detection algorithm must be compared against a reference standard; and a measure of validity must be calculable. Two independent reviewers will screen articles for inclusion, extract study details and assess risk of bias using QUADAS-2. Disagreements will be resolved by consensus or arbitration by a third reviewer. This protocol has been developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols checklist. ETHICS AND DISSEMINATION: This will be a review of previously published literature therefore no ethical approval is required. Results from this review will be published in a peer-reviewed journal. The results can be used in future research to identify occurrences of AECOPD. PROSPERO REGISTRATION NUMBER: CRD42019130863.

The Anterolateral Ligament of the Knee: Descriptive Anatomy and Clinical Correlation.

BACKGROUND: The anterolateral ligament is a fibrous structure in the anterolateral aspect of the knee. Recently this liagament of the knee has gained spotlight in anatomical and imaging studies and has been designated as a new ligament of the knee joint. The anterolateral ligament (ALL) has been postulated to be a restraint against the anterolateral instability of the knee resulting in a positive pivot shift test. The purpose of this study is to provide detailed anatomical characteristics of ALL in the Indian population. MATERIALS AND METHODS: The qualitative and quantitative characteristics of the ALL were observed in 20 embalmed cadaveric specimens. In all but one left male knee specimen (95%) ALL was observed. After isolating the ALL, its length, thickness, width, and points of attachments and dimensions of lateral collateral ligament (LCL) were determined. RESULTS: The ALL was consistently present in the anterolateral region of the knee separate from the joint capsule. Its proximal attachment to the femur is anterior and distal to the attachment of the LCL. Distally the superficial fibers of the ALL inserted close to the Gerdy's tubercle at the level of the fibular head, and the deeper fibers merged with the lateral meniscus. The mean length of the ALL was 43.35 mm ± 4.04 mm in flexion and 40.38 mm ± 4.35 mm in extension. The average width of the ALL was 6.98 mm ± 0.95 mm at its origin and 9.36 mm ± 1.07 mm at its insertion. CONCLUSION: The ALL is hypothesized to affect internal tibial rotation and plays a role in the pivot shift phenomenon. ALL rupture could be responsible for rotatory laxity after isolated intraarticular reconstruction of the ACL.

Stimuli-responsive hydrogels in drug delivery and tissue engineering.

Hydrogels are the three-dimensional network structures obtained from a class of synthetic or natural polymers which can absorb and retain a significant amount of water. Hydrogels are one of the most studied classes of polymer-based controlled drug release. These have attracted considerable attention in biochemical and biomedical fields because of their characteristics, such as swelling in aqueous medium, biocompatibility, pH and temperature sensitivity or sensitivity towards other stimuli, which can be utilized for their controlled zero-order release. The hydrogels are expected to explore new generation of self-regulated delivery system having a wide array of desirable properties. This review highlights the exciting opportunities and challenges in the area of hydrogels. Here, we review different literatures on stimuli-sensitive hydrogels, such as role of temperature, electric potential, pH and ionic strength to control the release of drug from hydrogels.

Treatment of Large Periapical Cyst Like Lesion: A Noninvasive Approach: A Report of Two Cases.

Periapical lesions develop as sequelae to pulp disease. Periapical radiolucent areas are generally diagnosed either during routine dental radiographic examination or following acute toothache. Various methods can be used in the nonsurgical management of periapical lesions: the conservative root canal treatment, decompression technique, active nonsurgical decompression technique, aspiration-irrigation technique, method using calcium hydroxide, lesion sterilization and repair therapy and the apexum procedure. Monitoring the healing of periapical lesions is essential through periodic follow-up examinations. The ultimate goal of endodontic therapy should be to return the involved teeth to a state of health and function without surgical intervention. All inflammatory periapical lesions should be initially treated with conservative nonsurgical procedures. Surgical intervention is recommended only after nonsurgical techniques have failed. Besides, surgery has many drawbacks, which limit its use in the management of periapical lesions. How to cite this article: Sood N, Maheshwari N, Gothi R, Sood N. Treatment of Large Periapical Cyst Like Lesion: A Noninvasive Approach: A Report of Two Cases. Int J Clin Pediatr Dent 2015;8(2):133-137.

DEVELOPMENT AND CHARACTERIZATION OF GLUCOSE SENSITIVE HYDROGELS FOR THE TREATMENT OF DIABETES MELLIT.

Development of stimuli-sensitive hydrogels for the delivery of drug involves the development of matrices that are glucose-sensitive and have strong sensing properties so that the developed system can sense the level of glucose and release the medicament in response to blood glucose level. In the present study an attempt has been made to develop a glucose sensitive hydrogel system which modulates the release of an anti-diabetic drug in response to the blood glucose level in the body. The hydrogel system was prepared by gas foaming technique using chitosan and polyvinyl alcohol (PVA) as polymer and glutaraldehyde as cross-linking agent. Metformin was used as a drug candidate because of its short biological half life (6.25±0.5 hrs). The prepared glucose sensitive hydrogel system has characterized using different parameters. It was observed that hydrogel swelled and deswelled reversibly depending on the pH and glucose sensitivity of the medium and has suitable mechanical properties. In-vitro results showed that the enzymatically immobilized hydrogel was sensitive to both pH and glucose for effective release of drug. It was found that higher the concentration of glucose in the medium, higher the amount of drug released from the hydrogel. In vivo results showed that glucose oxidase leads to reduction in blood glucose level in response to variable glucose concentration in the body thus achieving the desired therapeutic levels in the body . The present study showed that glucose sensitive hydrogels not only are efficient in controlling the physiological blood glucose level but also provide for a sustained and controlled release of drugs having short biological half life.

A comparative evaluation of freeze dried bone allograft and decalcified freeze dried bone allograft in the treatment of intrabony defects: A clinical and radiographic study.

BACKGROUND: Ideal graft material for regenerative procedures is autogenous bone graft but the major disadvantage with this graft is the need for a secondary surgical site to procure donor material and the frequent lack of intraoral donor site to obtain sufficient quantities of autogenous bone for multiple or deep osseous defects. Hence, to overcome these disadvantages, bone allografts were developed as an alternative source of graft material. MATERIALS AND METHODS: In 10 patients with chronic periodontitis, 20 bilateral infrabony defects were treated with freeze dried bone allograft (FDBA-Group A) and decalcified freeze dried bone allograft (DFDBA-Group B). Clinical and radiographic parameters were assessed preoperatively and at 3 months and 6 months postoperatively. Data thus obtained was subjected to statistical analysis. RESULTS: Significant improvement in the reduction in probing depth and relative attachment level (RAL) from the baseline to 3 months to baseline to 6 months in group A and group B, which was statistically significant but no statistically significant reduction was seen between 3 months and 6 months. On inter-group comparison, no significant differences were observed at all-time points. In adjunct to the probing depth and RAL, the radiographic area of the defect showed a similar trend in intra-group comparison and no significant difference was seen on inter-group comparison at all-time points. CONCLUSIONS: Within the limitations of the current study, it can be concluded that DFDBA did not show any improvement in the clinical and radiographic parameters in the treatment of the intrabony defects as compared to FDBA.

Guarding the precious smile: incidence and prevention of injury in sports: a review.

The paper provides a review about the orofacial injuries sustained during sports and the options available to the athletes for their prevention. It was done with a purpose to determine three different aspects incidence of dental injury during sporting activities, role of mouthguards in preventing sports injury, types of mouthguards and their properties. From this review, it is clear that sports carry a considerable risk of injury, this is not only true for the contact sports such as rugby or kickboxing, but also for seemingly less dangerous sports such as football. Amongst the different types of mouthguards, the most acceptable and safe ones are the custom-fabricated mouthguards, in particular the pressure-laminated ones. In general, mouthguard usage is less than the dental profession would recommend. As much of progress has been made in this area, need for the use of mouthguard needs to be emphasized and promoted by the dental profession.

WITHDRAWN: An overview on stimuli responsive hydrogels as drug delivery system.

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A rare case of vanishing lung syndrome.

We describe here a rare case of Idiopathic Bullous Emphysema/Vanishing Lung Syndrome (VLS) in a 33-year-old male patient with a history of marijuana abuse who presents to the hospital with pleuritic chest pain thought to be due to pneumothorax based on the chest radiograph. This case emphasizes the need to obtain chest computed tomography in a relatively stable patient suspected of VLS to reduce the potential risk of overseeing a bronchopleural fistula.

Pulmonary Arteriovenous Malformation (AVM) Causing Tension Hemothorax in a Pregnant Woman Requiring Emergent Cesarean Delivery.

Pulmonary arteriovenous malformations (PAVMs), although most commonly congenital, are usually detected later in life. We present a case of a 25-year-old woman with no previous history of AVM or telangiectasia, who presented with life-threatening hypoxia, hypotension, and pleuritic chest pain in 36th week of gestation. Chest tube placement revealed 4 liters of blood. Patient was subsequently found to have bleeding pulmonary AVM as the source of hemothorax. Successful embolisation of the bleeding vessel followed by thoracoscopic evacuation of the organized clot relieved the hypoxia. Further screening for AVM revealed large splenic AVM for which patient underwent splenectomy in the coming months.

A case of worsening deep cerebral venous sinus thrombosis managed by intrasinus thrombolysis.

Cerebral venous sinus thrombosis (CVST) is an uncommon condition with severe consequences. Although we do not know the exact incidence and prevalence of CVST, it is an important diagnosis. Over the past decade, it has been diagnosed more frequently due to greater awareness and availability of noninvasive diagnostic techniques. Furthermore, routine diagnostic neuroimaging has been used to monitor the clinical progress of these patients, especially in deteriorating cases. In order to decrease morbidity and mortality, an understanding of CVST treatment options is important. Treatment of extensive intracranial venous sinus thrombosis with intrasinus infusion of recombinant tissue plasminogen activator (rt-PA) is relatively controversial as there are no clear guidelines in regards to appropriate therapeutic management. We report a case of successful intrasinus thrombolysis of deep cerebral sinus thrombosis (DCST) resulting in rapid radiographic improvement associated with complete clinical recovery.