Publications by authors named "P M S Bedi"

93 Publications

Pattern and Burden of Opioid-Related Hospitalizations in United States from 2016-2018.

Br J Clin Pharmacol 2021 Apr 15. Epub 2021 Apr 15.

Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH.

Aim: The current opioid crisis in the United States (U.S.) is a formidable challenge for the healthcare system, and the general population. Our objective is to characterize the burden of opioid-related disorders in an inpatient setting in the U.S. for the years 2016, 2017 and 2018 using the National Inpatient Sample (NIS).

Methods: A cross-sectional analysis of the NIS was performed to identify and analyze hospitalizations with an opioid-related diagnosis in 2016, 2017 and 2018. Descriptive statistics and regression models were utilized to define the demographics of the population of interest and measure the outcomes.

Results: We identified 962,900 discharges with opioid-related diagnosis in 2016, 982,710 in 2017 and 942,110 in 2018. Majority were < 60 years old, were found in residents of low-income zip codes and covered by Medicaid. The adjusted mean total hospitalization cost trended up from $12,828 (95% CI 12,547-13,108) in 2016, to $13,164.9 (95% CI 12,872.47 - 13,457.34) in 2017 and then to $13,626.65 (95% CI 13,325.95 - 13,927.34) in 2018. The adjusted mortality was highest in 2016; 2.26% (95% CI 2.16-2.35) and it trended down to 1.97% (95% CI 1.88-2.05) in 2017, and to 1.89% (95% CI 1.81-1.98) in 2018.

Conclusion: Opioid-related disorders cause a significant number of hospitalizations in the U.S. A large proportion of these patients are age < 60 years, lower household income, covered by Medicaid. Programs directed towards this specific group can help reduce the overall burden of hospitalizations.
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http://dx.doi.org/10.1111/bcp.14857DOI Listing
April 2021

Hyponatremia and Encephalopathy in a 55-Year-old Woman with Syndrome of Inappropriate Antidiuretic Hormone Secretion as an Isolated Presentation of SARS-CoV-2 Infection.

Am J Case Rep 2021 Mar 24;22:e930135. Epub 2021 Mar 24.

Department of Nephrology, Brookdale University Hospital Medical Center, Brooklyn, NY, USA.

BACKGROUND During the coronavirus disease 2019 (COVID-19) pandemic of 2020, varied presentations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. The present report is of a case of hyponatremia and encephalopathy due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) as the main presentation of SARS-CoV-2 infection in a 55-year-old woman. CASE REPORT A 55-year-old woman with type II diabetes mellitus presented with confusion and slurring of speech, with a temperature of 38.5°C, heart rate of 120 bpm, blood pressure of 159/81 mmHg, and oxygen saturation of 98% on room air. She did not have edema on examination. Laboratory testing showed a low sodium level of 116 mEq/L (reference range, 135-145 mEq/L) with urine osmolarity of 364 mOsm/kg, urinary sodium of 69 mEq/L, urinary potassium of 15.6 mEq/L, and serum osmolarity of 251 mOsm/kg. The patient had normal serum thyroid-stimulating hormone and cortisol levels. A chest X-ray should no pulmonary infiltrates nor did a lumbar puncture reveal signs of infection. A real-time SARS-CoV-2 polymerase chain reaction assay was positive for COVID-19. Brain imaging with computed tomography was negative for acute infarct, intracranial hemorrhage, and mass effect. Based on findings from laboratory testing and physical examination, a diagnosis of SIADH was made. The patient was treated with 3% hypertonic saline, followed by salt tablets and fluid restriction, with improvement in her clinical symptoms and serum sodium level. CONCLUSIONS The present report is of a rare but previously reported association with SARS-CoV-2 infection. Encephalopathy and hyponatremia associated with SIADH without pneumonia or other symptoms of infection should be an indication for testing for SARS-CoV-2 infection.
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http://dx.doi.org/10.12659/AJCR.930135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008969PMC
March 2021

Curious case of steroid responsive diffuse anterior horn cell disease associated with COVID-19 infection.

Neurol Sci 2021 Mar 22. Epub 2021 Mar 22.

Department of Neurology, BLK Super Speciality Hospital, New Delhi, India.

Covid-19-associated neurological manifestations are being reported with increased frequency throughout the world. In a study from China, symptoms referable to peripheral nervous system (PNS) were described in approximately 9% of hospitalized Covid-19 patients. Common PNS symptoms reported in the study were loss of taste/smell and muscle pains. With this communication, we expand the spectrum of PNS manifestations of Covid-19 infection by reporting an association of steroid responsive diffuse anterior horn cell disease with Covid-19 infection from a tertiary care centre in India. Neurological manifestations of Covid-19 are diverse, and our case which to best of my knowledge is the first case in literature to report an occurrence of steroid responsive diffuse anterior horn cell disease associated with Covid-19 infection, adds to the ever-increasing spectrum of neurological manifestations associated with this pandemic causing virus. Good response to steroid in our case serves to provide an insight into the possible pathogenesis of this manifestation and also paves the way for future therapeutic decisions related to this association.
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http://dx.doi.org/10.1007/s10072-021-05163-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982509PMC
March 2021

Paraneoplastic cerebellar degeneration as a presenting manifestation of non-Hodgkin's lymphoma.

Neurol Sci 2021 Feb 8. Epub 2021 Feb 8.

Department of Neurology, BLK Super Speciality Hospital, New Delhi, India.

Background: Paraneoplastic Cerebellar degeneration (PCD) is one of the classical paraneoplastic syndromes (PNS) which is characterised by subacute onset, progressive cerebellar ataxia and is usually associated with small cell lung carcinoma, adeno carcinoma of breast and ovary followed by Hodgkin's lymphoma.

Objective: We herein report a case of subacute onset, progressive cerebellar ataxia in a 37-year-old female, who on evaluation was found to have non-Hodgkin's lymphoma and experienced good clinical response to treatment.

Discussion: As compared to solid tumours, chances of association of PNS with Lymphomas is quite low and there are only few case reports in the literature showing association of PCD with non-Hodgkin's lymphoma. As PCD is one of the classical PNS, it is very important to identify subtle cerebellar manifestations in an otherwise apparently normal individual, as early diagnosis and aggressive treatment can immensely improve the mortality and morbidity associated with this syndrome.

Conclusion: This case signifies the importance of suspecting PNS as an important differential diagnosis in a young patient presenting with subacute onset progressive cerebellar ataxia and evaluating her extensively for malignancy in spite of no paraneoplastic antibody been detected as early diagnosis and treatment can lead to gratifying response. We do agree that 2 weeks follow up is a short time interval to determine whether the response was sustained or not, for which a long term follow up is required.
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http://dx.doi.org/10.1007/s10072-021-05046-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868521PMC
February 2021

Predictors of longitudinal outcomes for children using long-term noninvasive ventilation.

Pediatr Pulmonol 2021 May 14;56(5):1173-1181. Epub 2020 Dec 14.

Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Background: Noninvasive ventilation (NIV) is a first-line therapy for sleep-related breathing disorders and chronic respiratory insufficiency. Evidence about predictors that may impact long-term NIV outcomes, however, is scarce. The aim of this study is to determine demographic, clinical, and technology-related predictors of long-term NIV outcomes.

Methods: A 10-year multicentred retrospective review of children started on long-term continuous or bilevel positive airway pressure (CPAP or BPAP) in Alberta. Demographic, technology-related, and longitudinal clinical data were collected. Long-term outcomes examined included ongoing NIV use, discontinuation due to improvement in underlying conditions, switch to invasive mechanical ventilation (IMV) or death, patient/family therapy declination, transfer of services, and hospital admissions.

Results: A total of 622 children were included. Both younger age and CPAP use predicted higher likelihood for NIV discontinuation due to improvement in underlying conditions (p < .05 and p < .01). Children with upper airway disorders or bronchopulmonary dysplasia were less likely to continue NIV (p < .05), while presence of central nervous system disorders had a higher likelihood of hospitalizations (p < .01). The presence of obesity/metabolic syndrome and early NIV-associated complications predicted higher risk for NIV declination (p < .05). Children with more comorbidities or use of additional therapies required more hospitalizations (p < .05 and p < .01) and the latter also predicted higher risk for being switched to IMV or death (p < .001).

Conclusions: Demographic, clinical data, and NIV type impact long-term NIV outcomes and need to be considered during initial discussions about therapy expectations with families. Knowledge of factors that may impact long-term NIV outcomes might help to better monitor at-risk patients and minimize adverse outcomes.
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http://dx.doi.org/10.1002/ppul.25188DOI Listing
May 2021

Covid-19 associated Guillain-Barre Syndrome: Contrasting tale of four patients from a tertiary care centre in India.

Am J Emerg Med 2021 Jan 16;39:125-128. Epub 2020 Sep 16.

Department of Neurology, BLK Super Speciality Hospital, New Delhi, India.

Background: Globally, more than 12 million people have been infected with COVID -19 infection till date with more than 500,000 fatalities. Although, Covid-19 commonly presents with marked respiratory symptoms in the form of cough and dyspnoea, a neurotropic presentation has been described of late as well.

Objective: In this brief communication we report four cases of Covid-19 who presented to our hospital with features suggestive of Guillain-Barre Syndrome (GBS).

Discussion: The mechanisms by which SARS-CoV-2 causes neurologic damage are multifaceted, including direct damage to specific receptors, cytokine-related injury, secondary hypoxia, and retrograde travel along nerve fibres. The pathogenesis of GBS secondary to Covid-19 is not well understood. It is hypothesised that viral illnesses related GBS could be due to autoantibodies or direct neurotoxic effects of viruses.

Conclusion: Nervous system involvement in Covid-19 may have been grossly underestimated. In this era of pandemic, it is very important for the physicians to be aware of association of GBS with Covid-19, as early diagnosis and treatment of this complication could have gratifying results. To the best of our knowledge, this is the first such case series of Guillain-Barre Syndrome associated with Covid-19 to be reported from India.
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http://dx.doi.org/10.1016/j.ajem.2020.09.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493759PMC
January 2021

Acute Kidney Injury in COVID-19 Patients: An Inner City Hospital Experience and Policy Implications.

Am J Nephrol 2020 2;51(10):786-796. Epub 2020 Oct 2.

Division of Nephrology, Brookdale University Hospital and Medical Center, Brooklyn, New York, USA,

Background: Although diffuse alveolar damage and respiratory failure are the key features of coronavirus disease 2019 (COVID-19), the involvement of other organs such as the kidney has also been reported. The reports of the incidence of acute kidney injury (AKI) in COVID-19 patients vary widely. In this study, we report our unique experience with AKI in COVID-19 patients in a low socioeconomic and predominantly ethnic minority group and provide its incidence, risk factors, and prognosis to expand the current understanding of this complication.

Methods: In this single-center, retrospective cohort study, we analyzed the data of 469 COVID-19 patients admitted to the Brookdale University Hospital in Brooklyn, NY, from March 18 through April 23, 2020. Information regarding demographics, comorbidities, medications, clinical and laboratory data, and outcomes was collected from the electronic medical records. Both univariate and multivariate analyses were performed to determine the association of AKI with in-hospital mortality.

Results: The median age was 66 years (interquartile range [IQR] 25-75; range 19-101 years), and 268 (57.14%) patients were male. Estimated glomerular filtration rate (eGFR) as determined by the Modification of Diet in Renal Disease Study Equation was low (<60 mL/min/1.73 m2) in 207 (44.1%) patients. During hospitalization, 128 (27.3%) patients developed AKI, and the incidence was significantly higher in those patients presenting with a low eGFR (N = 81, 39.1%; p < 0.001). Male sex, hypertension, the use of angiotensin-converting enzyme inhibitors and non-steroidal anti-inflammatories, hemodynamic instability, mechanical ventilation, acute respiratory distress syndrome, and admission elevated ferritin, creatinine kinase, brain natriuretic peptide, and troponin 1 were identified as the risk factors for in-hospital AKI. Ninety-seven (28.45%) patients died in the non-AKI group versus 91 (71.1%) in the AKI group (p < 0.001). The Cox proportional hazard model after adjusting for age, gender, comorbidities, hemodynamic status, and PF ratio (arterial oxygen partial pressure [PaO2]/fractional inspired oxygen [FiO2]) determined that on admission, an elevated blood urea nitrogen (hazard ratio [HR]: 1.75; 95% confidence interval [CI] 1.23-2.48), a low eGFR (HR 1.43; CI 1.1-2.03), AKI stage 1 (HR 1.14; CI 0.64-2.03), AKI stage 2 (HR 1.86; CI 1.03-3.56), and AKI stage 3 (HR 2.1; CI 1.3-2.81) were independent risk factors for in-hospital mortality. Renal replacement therapy (RRT) did not improve survival in stage III AKI.

Conclusion: AKI in our hospitalized COVID-19 patients was common and carried a high mortality, especially in patients with AKI stage 3. RRT did not improve survival. Policy changes and planning for this high incidence of AKI in COVID-19 patients and its associated high mortality are necessary at the local and national levels.
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http://dx.doi.org/10.1159/000511160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573899PMC
November 2020

Most recent strategies targeting estrogen receptor alpha for the treatment of breast cancer.

Mol Divers 2021 Feb 4;25(1):603-624. Epub 2020 Sep 4.

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.

Breast cancer is the most prominent, frequently diagnosed and leading cause of death among women. Estrogen is an agonist of estrogen receptor alpha (ER-α), expressed in mammary glands and is responsible for initiating many signalling pathways that lead to differentiation and development of breast tissue. Any mutations in these signalling pathways result in irregular growth of mammary tissue, leading to the development of tumour or cancer. All these observations attract the attention of researchers to antagonize ER-α receptor either by developing selective estrogen receptor modulators or by selective estrogen receptor degraders. Therefore, this article provides a brief overview of various factors that are responsible for provoking breast cancer in women and design strategies recently used by the various research groups across the world for antagonizing or demodulating ER-α.
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http://dx.doi.org/10.1007/s11030-020-10133-yDOI Listing
February 2021

Xanthine oxidase inhibitors: patent landscape and clinical development (2015-2020).

Expert Opin Ther Pat 2020 Oct 14;30(10):769-780. Epub 2020 Sep 14.

Department of Pharmaceutical Sciences, Guru Nanak Dev University , Amritsar, Punjab, India.

Introduction: Xanthine oxidase (XO) is a molybdoflavoprotein that catalyzes the oxidative hydroxylation of purines to produce uric acid and reactive oxygen species. These reaction products can cause severe disease conditions like hyperuricemia which makes XO enzyme, an important therapeutic target in diseases like gout.

Areas Covered: Herein, patents from 2015 to 2020 are discussed to disclose the synthetic, as well as natural compounds, claimed to inhibit XO enzyme. The article also presents the last five years of clinical progression of some prominent XO inhibitors.

Expert Opinion: There has been considerable creativity in the discovery of novel XO inhibitors in the last five years that falls outside the purine scaffold. Along with the evaluation of synthetic compounds, natural compounds can also be an area of interest for the discovery of novel XO inhibitors. Based on the patent literature of last five years, we can expect a burst of novel alternate compounds in the near future which could have the ability to reduce the uric acid level, by inhibiting XO enzyme in patients, which at the moment are striving hard to fight against the dreadful disease condition like gout.
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http://dx.doi.org/10.1080/13543776.2020.1811233DOI Listing
October 2020

The value of coronal DWI in brainstem stroke diagnosis.

Clin Case Rep 2020 Jul 13;8(7):1309-1310. Epub 2020 Apr 13.

Department of Medicine UPMC East Monroeville PA USA.

Acute brainstem strokes can present a diagnostic challenge due to its variable clinical presentation. MRI with diffusion-weighted (axial) imaging is highly sensitive for diagnosing ischemic lesions however even that can fail to identify early lesions in the brainstem. Combining coronal section to standard axial MRI-DWI can facilitate early diagnosis in these cases.
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http://dx.doi.org/10.1002/ccr3.2847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364084PMC
July 2020

Rational approaches for the design of various GABA modulators and their clinical progression.

Mol Divers 2021 Feb 13;25(1):551-601. Epub 2020 Mar 13.

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, PB, 143005, India.

GABA (γ-amino butyric acid) is an important inhibitory neurotransmitter in the central nervous system. Attenuation of GABAergic neurotransmission plays an important role in the etiology of several neurological disorders including epilepsy, Alzheimer's disease, Huntington's chorea, migraine, Parkinson's disease, neuropathic pain, and depression. Increase in the GABAergic activity may be achieved through direct agonism at the GABA receptors, inhibition of enzymatic breakdown of GABA, or by inhibition of the GABA transport proteins (GATs). These functionalities make GABA receptor modulators and GATs attractive drug targets in brain disorders associated with decreased GABA activity. There have been several reports of development of GABA modulators (GABA receptors, GABA transporters, and GABAergic enzyme inhibitors) in the past decade. Therefore, the focus of the present review is to provide an overview on various design strategies and synthetic approaches toward developing GABA modulators. Furthermore, mechanistic insights, structure-activity relationships, and molecular modeling inputs for the biologically active derivatives have also been discussed. Summary of the advances made over the past few years in the clinical translation and development of GABA receptor modulators is also provided. This compilation will be of great interest to the researchers working in the field of neuroscience. From the light of detailed literature, it can be concluded that numerous molecules have displayed significant results and their promising potential, clearly placing them ahead as potential future drug candidates.
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http://dx.doi.org/10.1007/s11030-020-10068-4DOI Listing
February 2021

Monocarbonyl Curcumin-Based Molecular Hybrids as Potent Antibacterial Agents.

ACS Omega 2019 Jul 5;4(7):11673-11684. Epub 2019 Jul 5.

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab 143005, India.

Keeping in view various pharmacological attributes of curcumin, coumarin, and isatin derivatives, triazole-tethered monocarbonyl curcumin-coumarin and curcumin-isatin molecular hybrids have been synthesized and evaluated for their antibacterial potential against Gram-positive ( and ) and Gram-negative ( and ) human pathogenic bacterial strains. Among all hybrid molecules, and showed the most potent antibacterial activity with inhibition zones of 29 and 31 mm along with MIC values of 12.50 and 6.25 μg/mL, respectively. Structure-activity relationship that emerged from biological data revealed that the two-carbon alkyl chain between triazole and coumarin/isatin moiety is well tolerable for the activity. Bromo substitution at the fifth position of isatin, para-cholo substitution in the case of curcumin-isatin, and para-methoxy in the case of curcumin-coumarin hybrids on ring A of curcumin are most suitable groups for the antibacterial activity. Various types of binding interactions of and within the active site of dihydrofolate reductase (DHFR) of are also streamlined by molecular modeling studies, suggesting their capability in completely blocking DHFR.
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http://dx.doi.org/10.1021/acsomega.9b01109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682034PMC
July 2019

Updates in Treatment of Recurrent Infection.

J Clin Med Res 2019 Jul 11;11(7):465-471. Epub 2019 Jun 11.

Department of Medicine, UPMC East, Monroeville, PA 15146, USA.

Recurrent infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.
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http://dx.doi.org/10.14740/jocmr3854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6575119PMC
July 2019

Cardiac Arrest Due to Benzonatate Overdose.

Am J Case Rep 2019 May 3;20:640-642. Epub 2019 May 3.

Division of Nephrology, Brookdale University Hospital and Medical Center, Brooklyn, NY, USA.

BACKGROUND Benzonatate is one of the most widely prescribed nonnarcotic antitussives to relieve cough symptoms. As a structurally similar agent to other local anesthetics, including tetracaine and procaine, the risk to the public is not fully appreciated. CASE REPORT A 37-year-old female presented to the Emergency Department (ED) status post cardiac arrest. Advanced cardiac life support (ACLS) protocol was performed, and return of spontaneous circulation (ROSC) was achieved. Total downtime was 30 minutes. The patient was intubated, sedated, and hypothermia protocol was initiated. The patient developed bradyarrhythmia and mild coagulopathy suspicious for disseminated intravascular coagulation (DIC), thus hypothermia protocol was terminated later. A review of laboratory data showed acidosis with pH of 6.87, mixed acidosis secondary to high anion gap metabolic and respiratory acidosis with elevated liver enzymes. It was reported that approximately 2 hours prior to her presentation; the patient had ingested less than 30 pills of benzonatate 200 mg capsules with alcohol. CONCLUSIONS Ingestion of benzonatate, a widely prescribed antitussive, may pose a risk to patients due to the potential for rapid development of life-threatening adverse events and limited treatment options in the overdose setting, not only in children but also in adults. Rational prescribing and patient education are needed.
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http://dx.doi.org/10.12659/AJCR.915151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512753PMC
May 2019

Chimeric Antigen Receptor T-Cells: The Future is Now.

J Clin Med 2019 Feb 7;8(2). Epub 2019 Feb 7.

Department of Medicine, Northside Hospital Cancer Institute, Atlanta, GA 30342, USA.

The immune system acting via cancer immune-surveillance is considered a potential target for improving outcomes among some malignancies. The ability to harness immune cells, engineer them and educate them to target cancer cells has changed the paradigm for treating non-Hodgkin's lymphomas (NHL) and acute lymphoblastic leukemia (ALL). Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable anti-tumor activity against refractory B cell malignancies. Ongoing research aims to expand the scope of this adoptive cell therapy, understanding mechanisms of resistance and reducing toxicity. In this review, we will discuss the current scope of CAR T-cell therapy and ongoing future applications.
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http://dx.doi.org/10.3390/jcm8020207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406995PMC
February 2019

British Thoracic Society guideline for bronchiectasis in adults.

BMJ Open Respir Res 2018 28;5(1):e000348. Epub 2018 Dec 28.

Host Defence Unit, Department of Respiratory Medicine, Royal Brompton and Harefield NHS Foundation Trust, London, UK.

The full British Thoracic Society Guideline for Bronchiectasis in Adults is published in . The following is a summary of the recommendations and good practice points. The sections referred to in the summary refer to the full guideline. The appendices are available in the full guideline.
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http://dx.doi.org/10.1136/bmjresp-2018-000348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6326298PMC
December 2018

Validation of the Incremental Shuttle Walk Test as a Clinical End Point in Bronchiectasis.

Chest 2018 12 6;154(6):1321-1329. Epub 2018 Oct 6.

MRC Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom; Department of Respiratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.

Background: A validated clinical end point is needed to assess response to therapies in bronchiectasis.

Objectives: The goal of this study was to assess the reliability, validity, and responsiveness of the incremental shuttle walk test (ISWT) as a clinical end point in bronchiectasis.

Methods: In clinically stable patients (n = 30), the ISWT was performed twice, 6 months apart. Correlation between the St. George's Respiratory Questionnaire (SGRQ) and the ISWT (n = 94) was performed. The 1-year gentamicin study was reanalyzed to assess the area under the curve (percent change of ISWT with a ≥ 4 unit improvement in total SGRQ). ISWT was performed prior to and following 14 days of antibiotics for an exacerbation (94 oral courses and 30 IV courses, n = 124) and reanalysis of the 1-year gentamicin study (n = 57).

Results: The ISWT did not significantly change over 6 months while clinically stable. The ISWT correlated inversely with the SGRQ (rs = -0.60; P < .0001), Bronchiectasis Severity Index score (rs = -0.44; P < .0001), and sedentary time (rs = -0.48; P = .0007) but correlated with physical activity (rs = 0.42; P = .004). The area under the curve for percent change in ISWT with ≥ 4 unit improvement in SGRQ was 0.79 (95% CI, 0.66-0.91; P = .001). A threshold of 5% improvement in the ISWT had a 92% sensitivity but 50% specificity, and from the responsiveness studies would capture 73% of all patients.

Conclusions: This study confirmed the ISWT to be reliable, valid, and responsive to change in patients with bronchiectasis. The authors propose that a minimum clinically important difference of 5% improvement in the ISWT would be a useful objective end point to assess therapies in bronchiectasis.
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http://dx.doi.org/10.1016/j.chest.2018.09.019DOI Listing
December 2018

Paroxysmal Sympathetic Hyperactivity after Cardiac Arrest in a Young Male.

Cureus 2018 Jul 22;10(7):e3028. Epub 2018 Jul 22.

Internal Medicine, Rochester General Hospital, Rochester, USA.

Paroxysmal sympathetic hyperactivity (PSH) is a syndrome of an increased sympathetic drive after brain injury. PSH has been previously referred with multiple different names. It is seen most commonly after a traumatic brain injury, but rarely it has been reported after infections, brain malignancies, and brain injury after cardiac arrest. We present a case of a young male who developed PSH after cardiac arrest and will discuss clinical features and various management options.
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http://dx.doi.org/10.7759/cureus.3028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150751PMC
July 2018

Pentoxifylline protects against loss of function and renal interstitial fibrosis in chronic experimental partial ureteral obstruction.

Pathophysiology 2018 Dec 23;25(4):419-425. Epub 2018 Aug 23.

Division of Nephrology & Hypertension, The Brookdale University Hospital & Medical Center, One Brookdale Plaza, Brooklyn, NY, 11212, United States. Electronic address:

Tubulointerstitial fibrosis (TIF) is a hallmark of chronic kidney disease resulting from diverse etiologies and predicts severity and progression of the kidney disease. To investigate the pathogenesis of TIF, complete unilateral ureteral obstruction (UUO) is the most widely used animal model. However, UUO precludes evaluation of renal function. In the present study, we created a rat model of chronic partial ureteral obstruction (PUO), which allowed assessment of renal function at different intervals after obstruction. We examined the effects of pentoxifylline (PTF), a phosphodiesterase inhibitor used clinically to treat peripheral artery disease, on renal function and TIF. Studies were performed in sham-PUO rats and rats with 14-day PUO or 30-day PUO receiving vehicle in drinking water or PTF (400 mg/liter in drinking water). At day-14 PUO, glomerular filtration rate (GFR) was markedly and similarly depressed in rats receiving vehicle or PTF as compared with sham-operated rats. However, at day-30 PUO, GFR in rats receiving PTF was significantly higher than that in rats receiving vehicle, approaching the level seen in the sham-operated rats. At day-30 PUO, histologic studies also revealed a marked reduction of TIF in rats treated with PTF as compared with the rats receiving vehicle in drinking water. Western blot analysis demonstrated that at day-30 the expression of α-smooth muscle actin (an indicator of renal fibrosis) in the medulla was significantly reduced in PUO rats treated with PTF. In conclusion, PTF treatment ameliorated renal fibrosis and helped preserve renal function in a rodent model of PUO.
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http://dx.doi.org/10.1016/j.pathophys.2018.08.004DOI Listing
December 2018

Estradiol attenuates ischemia reperfusion-induced acute kidney injury through PPAR-γ stimulated eNOS activation in rats.

Mol Cell Biochem 2019 Mar 7;453(1-2):1-9. Epub 2018 Sep 7.

Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.

We investigated the involvement of peroxisome proliferator activated receptor-γ (PPAR-γ)/endothelial nitric oxide synthase (eNOS) pathway in estradiol mediated protection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats. To induce AKI, rats underwent 40 min of bilateral renal ischemia followed by 24 h of reperfusion. I/R-induced kidney damage was quantified by measuring serum creatinine, creatinine clearance, urea nitrogen, uric acid, potassium, fractional excretion of sodium, microproteinuria, and renal oxidative stress (thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione). Hematoxylin eosin stain demonstrated renal histology, while renal expression of apoptotic markers (Bcl-2, Bax), PPAR-γ and eNOS were quantified by immunohistochemistry. Estradiol (1 mg/kg, i.p.) was administered 30 min before I/R in rats. In separate groups, PPAR-γ antagonist, BADGE (30 mg/kg, i.p.), and NOS inhibitor, L-NAME (20 mg/kg, i.p.) were administered prior to estradiol treatment, which was followed by I/R in rats. I/R caused significant renal damage as demonstrated by biochemical (serum/urine), renal oxidative stress and histological changes alongwith increased expression of Bax and decreased levels of Bcl-2, PPAR-γ and eNOS, which were prevented by estradiol. Pre-treatment with BADGE and L-NAME abolished estradiol mediated renoprotection. Notably, I/R + estradiol + BADGE group revealed decreased expression of PPAR-γ and eNOS in renal tissues. In I/R + estradiol + L-NAME group, eNOS expression was reduced while PPAR-γ levels remained unchanged. These results suggest that estradiol modulates PPAR-γ which consequently regulates eNOS expression in rat kidneys. We conclude that estradiol protects against I/R-induced AKI through PPAR-γ stimulated eNOS activation in rats.
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http://dx.doi.org/10.1007/s11010-018-3427-4DOI Listing
March 2019

5,6-Benzoflavones as cholesterol esterase inhibitors: synthesis, biological evaluation and docking studies.

Medchemcomm 2018 Mar 19;9(3):490-502. Epub 2018 Jan 19.

Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab 143005 , India . Email: ; Tel: +919463148367 ; Tel: +919815698249.

In a continued effort to develop potent cholesterol esterase (CEase) inhibitors, a series of 5,6-benzoflavone derivatives was rationally designed and synthesized by changing the position of the benzene ring attached to the flavone skeleton in previously reported 7,8-benzoflavones. All the synthesized compounds were checked for their inhibitory potential against cholesterol esterase (CEase) using a spectrophotometric assay. Among the series of forty compounds, seven derivatives (- to -) exhibited above 90 percent inhibition against CEase in an enzymatic assay. Compound - showed the most promising activity with an IC value of 0.73 nM against cholesterol esterase. To determine the type of inhibition, enzyme kinetic studies were carried out for -, which revealed its mixed-type inhibition approach. Moreover, to figure out the key binding interactions of - with the amino acid residues of the enzyme's active site, molecular protein-ligand docking studies were also performed. - completely blocks the catalytic assembly of CEase and prevents it from participating in the ester hydrolysis mechanism. The favorable binding conformation of - suggests its prevailing role as a CEase inhibitor. Overall, the study showed that the -orientation of ring A with respect to the carbonyl group of ring C is responsible for the potent CEase inhibitory activity of the newly synthesized compounds.
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http://dx.doi.org/10.1039/c7md00565bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072486PMC
March 2018

The impact of acute air pollution fluctuations on bronchiectasis pulmonary exacerbation: a case-crossover analysis.

Eur Respir J 2018 07 27;52(1). Epub 2018 Jul 27.

Scottish Centre for Respiratory Research, University of Dundee, Dundee, UK.

In bronchiectasis, exacerbations are believed to be triggered by infectious agents, but often no pathogen can be identified. We hypothesised that acute air pollution exposure may be associated with bronchiectasis exacerbations.We combined a case-crossover design with distributed lag models in an observational record linkage study. Patients were recruited from a specialist bronchiectasis clinic at Ninewells Hospital, Dundee, UK.We recruited 432 patients with clinically confirmed bronchiectasis, as diagnosed by high-resolution computed tomography. After excluding days with missing air pollution data, the final model for particles with a 50% cut-off aerodynamic diameter of 10 µm (PM) was based on 6741 exacerbations from 430 patients and for nitrogen dioxide (NO) it included 6248 exacerbations from 426 patients. For each 10 µg·m³ increase in PM and NO, the risk of having an exacerbation that same day increased significantly by 4.5% (95% CI 0.9-8.3) and 3.2% (95% CI 0.7-5.8) respectively. The overall (lag zero to four) increase in risk of exacerbation for a 10 μg·m increase in air pollutant concentration was 11.2% (95% CI 6.0-16.8) for PM and 4.7% (95% CI 0.1-9.5) for NO Subanalysis showed higher relative risks during spring (PM 1.198 (95% CI 1.102-1.303), NO 1.146 (95% CI 1.035-1.268)) and summer (PM 2.142 (95% CI 1.785-2.570), NO 1.352 (95% CI 1.140-1.602)) when outdoor air pollution exposure would be expected to be highest.In conclusion, acute air pollution fluctuations are associated with increased exacerbation risk in bronchiectasis.
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http://dx.doi.org/10.1183/13993003.02557-2017DOI Listing
July 2018

Effectiveness of Activity-Based Therapy in Comparison with Surface Spinal Stimulation in People with Traumatic Incomplete Spinal Cord Injury for Activation of Central Pattern Generator for Locomotion: Study Protocol for a 24-Week Randomized Controlled Trial.

Asian Spine J 2018 Jun 4;12(3):503-510. Epub 2018 Jun 4.

Department of Spine Services, Indian Spinal Injuries Centre, New Delhi, India.

Study Design: A multi-centric randomized controlled trial to be conducted at two sites, department of phyhysiotherapypy, Punjabi University, Patiala and rehabilitation department, Indian Spinal Injury Centre, New Delhi, India.

Purpose: To determine the effectiveness of activity-based therapy in comparison with surface spinal stimulation (SSS) in traumatic incomplete spinal cord injury (SCI) with special reference to locomotion-a central pattern generator controlled function.

Overview Of Literature: A major goal for many patients after SCI is to regain the function of locomotion. It is crucial that rehabilitation strives to maximize locomotor ability and functional recovery after SCI. Experimental evidence of improvement in stepping and motor control after activity-based training in animal models and human SCI has been translated into clinical neuro-rehabilitation.

Methods: Control group participants will undertake an intensive 24-week duration thrice weekly program of activity-based therapy. In addition to this the participants in experimental group will also receive a session of 45 minutes of SSS on thrice weekly basis. The primary analysis for our study will be at 24 weeks. Linear regression will be used to determine the mean between-group differences and 95% confidence interval for all continuous outcomes using baseline scores and group allocation as covariates.

Results: The primary outcome measure is improvement in the level of walking index for SCI-II. The secondary outcome measures are modified Ashworth scale, Penn spasm frequency score, spinal cord independence measure-III, SCI functional ambulation inventory, Hoffman's reflex, somatosensory evoked potential, and American Spinal Injury Association Impairment Scale scores.

Conclusions: An insight into training-induced mechanisms will be of great importance to fine tune such combined treatments and vindicate their efficacy in restoration of locomotion and functional activities in individuals with SCI.
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http://dx.doi.org/10.4184/asj.2018.12.3.503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002180PMC
June 2018

Blood Neutrophils Are Reprogrammed in Bronchiectasis.

Am J Respir Crit Care Med 2018 10;198(7):880-890

1 MRC Centre for Inflammation Research at the University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom; and.

Rationale: Excessive neutrophilic airway inflammation is the central feature of bronchiectasis, but little is known about neutrophils in bronchiectasis.

Objectives: To assess blood neutrophil phenotype in patients with bronchiectasis while stable and during exacerbations.

Methods: In the clinically stable arm of this study, there were eight healthy volunteers, eight patients with mild bronchiectasis, and eight patients with severe bronchiectasis. In addition, six patients with severe bronchiectasis were compared with six patients with community-acquired pneumonia at the start and end of an exacerbation. We assessed neutrophils for spontaneous apoptosis, cell surface marker expression, degranulation, reactive oxygen species generation, phagocytosis, and killing of Pseudomonas aeruginosa (PAO1). In addition, blood neutrophil function was compared with airway neutrophil function in bronchiectasis.

Measurements And Main Results: In stable bronchiectasis, compared with healthy volunteers, blood neutrophils had significantly prolonged viability, delayed apoptosis, increased CD62L shedding, upregulated CD11b expression, increased myeloperoxidase release, and impaired neutrophil phagocytosis and killing of PAO1. Bronchiectatic airway neutrophils had significantly lower bacterial phagocytosis and killing than their matched autologous blood neutrophils. Both blood and airway neutrophil phagocytosis and killing were impaired at the start of an exacerbation and improved following antibiotic treatment. In pneumonia, there was a significant improvement in phagocytosis and killing after treatment with antibiotics. During infections, there was no difference in phagocytosis, but there was significantly increased bacterial killing at the start and end of infection in pneumonia compared with bronchiectasis exacerbations.

Conclusions: In bronchiectasis stable state, peripheral blood neutrophils are reprogrammed and have prolonged survival. This impairs their functional ability of bacterial phagocytosis and killing, thereby perpetuating the vicious circle in bronchiectasis.
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http://dx.doi.org/10.1164/rccm.201712-2423OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173062PMC
October 2018

Blastic plasmacytoid dendritic cell neoplasm.

Clin Case Rep 2018 04 4;6(4):770-772. Epub 2018 Mar 4.

Sparrow Hospital 1215 E Michigan Ave Lansing Michigan 48912.

Blastic plasmacytoid dendritic cell neoplasm is an aggressive neoplasm with a median survival of only a few months despite treatment. An exhaustive immunohistochemical workup is required to differentiate it from myeloid sarcoma and extranodal NK/T cell lymphoma. Treatment is with induction using a regimen utilized for leukemia. Allogeneic hematopoietic stem cell transplantation is recommended for those who achieve remission following induction.
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http://dx.doi.org/10.1002/ccr3.1457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889251PMC
April 2018

Angioimmunoblastic T-cell lymphoma: a rare subtype of peripheral T-cell lymphoma.

Clin Case Rep 2018 04 10;6(4):750-752. Epub 2018 Feb 10.

Michigan State University/Sparrow hospital B301, 788 Service Road East Lansing Michigan 48824.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare form of NHL and usually presents in the late stage due to the atypical laboratory findings. Immunohistochemistry of the lymph node in AITL is characterized by positive CD2, CD3, CD4, CD10, CXCL-13, PD1 often BCL-6 and CD20 positive. Meshworks of follicular dendritic cells are seen outside follicles with CD21 and CD23 stains. EBV can be often positive as well. Autologous transplantation should be offered in the first remission as poor outcome is reported with anthracycline-containing regimens.
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http://dx.doi.org/10.1002/ccr3.1388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889216PMC
April 2018

CK 20-positive and CK 7-negative Merkel cell carcinoma of the cheek.

Clin Case Rep 2018 03 1;6(3):549-550. Epub 2018 Feb 1.

Sparrow Hospital 1215 E Michigan Ave Lansing Michigan 48912.

Merkel cell carcinomas (MCCs) are uncommon, highly malignant skin tumors that develop in sun-exposed areas of the skin. Most of the MCCs are CK 20-positive and CK 7-negative such as our case. About 80% of Merkel cell carcinoma is associated with Merkel cell polyomavirus.
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http://dx.doi.org/10.1002/ccr3.1383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838268PMC
March 2018