Publications by authors named "Rohit Gupta"

192 Publications

Intracranial mesenchymal tumors with FET-CREB fusion are composed of at least two epigenetic subgroups distinct from meningioma and extracranial sarcomas.

Brain Pathol 2021 Nov 25:e13037. Epub 2021 Nov 25.

Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.

'Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of solitary fibrous tumor and AFH of extracranial soft tissue, whereas the second epigenetic subgroup (Group B, 4 tumors) clustered nearest to but independent of CCS and also lacked expression of melanocytic markers (HMB45, Melan A, or MITF) characteristic of CCS. Group A tumors most often occurred in adolescence or early adulthood, arose throughout the neuroaxis, and contained mostly EWSR1-ATF1 and EWSR1-CREB1 fusions. Group B tumors arose most often in early childhood, were located along the cerebral convexities or spinal cord, and demonstrated an enrichment for tumors with CREM as the fusion partner (either EWSR1-CREM or FUS-CREM). Group A tumors more often demonstrated stellate/spindle cell morphology and hemangioma-like vasculature, whereas Group B tumors more often demonstrated round cell or epithelioid/rhabdoid morphology without hemangioma-like vasculature, although robust comparison of these clinical and histologic features requires future study. Patients with Group B tumors had inferior progression-free survival relative to Group A tumors (median 4.5 vs. 49 months, p = 0.001). Together, these findings confirm that intracranial AFH-like neoplasms and IMMT represent histologic variants of a single tumor type ('intracranial mesenchymal tumor, FET-CREB fusion-positive') that is distinct from meningioma and extracranial sarcomas. Additionally, epigenomic evaluation may provide important prognostic subtyping for this unique tumor entity.
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http://dx.doi.org/10.1111/bpa.13037DOI Listing
November 2021

Management of Advanced Pulmonary Sarcoidosis.

Am J Respir Crit Care Med 2021 Nov 23. Epub 2021 Nov 23.

University of Cincinnati Medical Center, 24267, Medicine, Cincinnati, Ohio, United States.

The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "Advanced Pulmonary Sarcoidosis" (APS) which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. While APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes including death. Herein we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.
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http://dx.doi.org/10.1164/rccm.202106-1366CIDOI Listing
November 2021

Assessing dermatology resident confidence in caring for patients with skin of color.

Clin Dermatol 2021 Sep-Oct;39(5):873-878. Epub 2021 Aug 20.

Department of Dermatology, The University of Texas Health Science Center at Houston, Houston, Texas, USA.

Many dermatology residency programs lack sufficient didactics and experiences with patients with skin of color (SOC). This may impact resident confidence with this patient population, which may affect patient satisfaction and perceptions of care. Dermatology residents nationwide were surveyed to determine their confidence in care of patients with SOC and white skin across several dimensions, including detailing morphology, making diagnostic and therapeutic decisions, tailoring treatment recommendations, and detecting suspicious lesions. A total of 125 dermatology residents representing 46 programs (of 119, 39%) responded. Resident confidence was significantly lower across all categories measured regarding caring for patients with SOC compared with patients with white skin (P <.001). After multivariate analysis adjusting for demographic and residency program characteristics, confidence in caring for patients with SOC remained significantly lower. Residents in programs with SOC education (i.e., SOC didactics, SOC clinical rotation) reported significantly higher confidence in one or more aspects of SOC care compared with residents in programs without such curricula. A deficiency in SOC education may contribute to the lower resident confidence observed. Integrating only one type of SOC education into residents' curricula, although helpful, may not sufficiently enhance confidence across all dimensions of care. A multifaceted approach is needed.
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http://dx.doi.org/10.1016/j.clindermatol.2021.08.019DOI Listing
November 2021

Constipation and Postprandial Pain in a Patient With Shortness of Breath.

Fed Pract 2021 Jul;38(7):325-327

is a Certified Physician Assistant at Santa Clara Valley Medical Center in San Jose, California. is a Medical Student at Baylor College of Medicine in Houston, Texas. is a Physician Assistant at the Michael E. DeBakey Veterans Affairs (VA) Medical Center in Houston, Texas. is an Assistant Professor of Surgery at Baylor College of Medicine and Deputy Chief Medical Officer for the VA Veterans Integrated Services Network 16.

Incidental image findings may be important for resolving seemingly unrelated symptoms at presentation.
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http://dx.doi.org/10.12788/fp.0154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560112PMC
July 2021

Left-Sided Amyand Hernia: Case Report and Review of the Literature.

Fed Pract 2021 Jun;38(6):286-290

and are Medical Students at Baylor College of Medicine in Houston, Texas. is Deputy Chief Medical Officer for Quality and Safety for US Department of Veterans Affairs Veterans Integrated Service Network 16 in Houston.

Left-sided Amyand hernia is a rare condition that requires a high degree of clinical suspicion to correctly diagnose.
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http://dx.doi.org/10.12788/fp.0136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8560049PMC
June 2021

Differential regulation of miR-21-5p delays wound healing of melanocyte-deprived vitiligo skin by modulating the expression of tumor-suppressors PDCD4 and Maspin.

J Cell Physiol 2021 Oct 22. Epub 2021 Oct 22.

Skin Biology Laboratory, CSIR-Institute of Genomics and Integrative Biology, New Delhi, India.

The loss of melanocytes in vitiligo is associated with architectural, transcriptional, and cellular perturbations of keratinocytes and manifests as a reduced proliferation potential in vitro and delayed re-epithelialization in vivo. To understand the molecular mechanisms underlying this delay, microRNA (miRNA) profiling was performed on split skin biopsies collected on Day 1 (basal level) and Day 14 (wound re-epithelialization) from nonlesional (NL) and lesional (L) skin of five subjects with stable nonsegmental vitiligo and 129 miRNAs were found to be differentially regulated between the NL and L healed epidermis. miR-21-5p, expressed at comparable levels on NL and L Day 1 samples, demonstrated significant upregulation during re-epithelialization. However, the extent of its upregulation was relatively lower in L (10 times compared to Day 1) as compared to NL skin (17 times compared to Day 1). The overexpression of miR-21 in keratinocytes led to a significant increase in the expression of proliferation markers (Ki67 and MCM6 messenger RNA, Ki67 positivity), along with an increase in keratinocyte migration. Using a small interfering RNA mediated knockdown approach, we further demonstrated that miR-21-5p mediates its effects by suppressing the expression of programmed cell death 4 (PDCD4) and mammary serine protease inhibitor (Maspin), both tumor-suppressor genes. Investigation of clinical samples corroborated the lower miR-21 levels and a higher expression of PDCD4 and Maspin in L Day 14 compared to the NL Day 14 epidermis. In conclusion, this study revealed that a relatively lower upregulation of miR-21-5p in L skin leads to significantly higher levels of PDCD4 and Maspin, delaying wound re-epithelialization by reducing the proliferation and migration of keratinocytes.
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http://dx.doi.org/10.1002/jcp.30614DOI Listing
October 2021

Association of abnormal pulmonary vasculature on CT scan for COVID-19 infection with decreased diffusion capacity in follow up: A retrospective cohort study.

PLoS One 2021 15;16(10):e0257892. Epub 2021 Oct 15.

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, United States of America.

Background: Coronavirus Disease 2019 (COVID-19) is a respiratory viral illness causing pneumonia and systemic disease. Abnormalities in pulmonary function tests (PFT) after COVID-19 infection have been described. The determinants of these abnormalities are unclear. We hypothesized that inflammatory biomarkers and CT scan parameters at the time of infection would be associated with abnormal gas transfer at short term follow-up.

Methods: We retrospectively studied subjects who were hospitalized for COVID-19 pneumonia and discharged. Serum inflammatory biomarkers, CT scan and clinical characteristics were assessed. CT images were evaluated by Functional Respiratory Imaging with automated tissue segmentation algorithms of the lungs and pulmonary vasculature. Volumes of the pulmonary vessels that were ≤5mm (BV5), 5-10mm (BV5_10), and ≥10mm (BV10) in cross sectional area were analyzed. Also the amount of opacification on CT (ground glass opacities). PFT were performed 2-3 months after discharge. The diffusion capacity of carbon monoxide (DLCO) was obtained. We divided subjects into those with a DLCO <80% predicted (Low DLCO) and those with a DLCO ≥80% predicted (Normal DLCO).

Results: 38 subjects were included in our cohort. 31 out of 38 (81.6%) subjects had a DLCO<80% predicted. The groups were similar in terms of demographics, body mass index, comorbidities, and smoking status. Hemoglobin, inflammatory biomarkers, spirometry and lung volumes were similar between groups. CT opacification and BV5 were not different between groups, but both Low and Normal DLCO groups had lower BV5 measures compared to healthy controls. BV5_10 and BV10 measures were higher in the Low DLCO group compared to the normal DLCO group. Both BV5_10 and BV10 in the Low DLCO group were greater compared to healthy controls. BV5_10 was independently associated with DLCO<80% in multivariable logistic regression (OR 1.29, 95% CI 1.01, 1.64). BV10 negatively correlated with DLCO% predicted (r = -0.343, p = 0.035).

Conclusions: Abnormalities in pulmonary vascular volumes at the time of hospitalization are independently associated with a low DLCO at follow-up. There was no relationship between inflammatory biomarkers during hospitalization and DLCO. Pulmonary vascular abnormalities during hospitalization for COVID-19 may serve as a biomarker for abnormal gas transfer after COVID-19 pneumonia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257892PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519442PMC
November 2021

SARS-CoV-2 detection with aptamer-functionalized gold nanoparticles.

Talanta 2022 Jan 1;236:122841. Epub 2021 Sep 1.

Department of Mechanical Engineering, McMaster University, Hamilton, Ontario, Canada; School of Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada; Department of Materials Science and Engineering, McMaster University, Hamilton, Ontario, Canada. Electronic address:

A rapid detection test for SARS-CoV-2 is urgently required to monitor virus spread and containment. Here, we describe a test that uses nanoprobes, which are gold nanoparticles functionalized with an aptamer specific to the spike membrane protein of SARS-CoV-2. An enzyme-linked immunosorbent assay confirms aptamer binding with the spike protein on gold surfaces. Protein recognition occurs by adding a coagulant, where nanoprobes with no bound protein agglomerate while those with sufficient bound protein do not. Using plasmon absorbance spectra, the nanoprobes detect 16 nM and higher concentrations of spike protein in phosphate-buffered saline. The time-varying light absorbance is examined at 540 nm to determine the critical coagulant concentration required to agglomerates the nanoprobes, which depends on the protein concentration. This approach detects 3540 genome copies/μl of inactivated SARS-CoV-2.
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http://dx.doi.org/10.1016/j.talanta.2021.122841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409056PMC
January 2022

Hepatitis C virus subtyping in Uttarakhand, India: a comparative study.

Virusdisease 2021 Sep 17;32(3):576-581. Epub 2021 Aug 17.

Department of Microbiology, All India Institute of Medical Sciences, Veerbhadra Marg, Dehradun, Rishikesh, 249203 Uttarakhand India.

The objective of this study was to compare Reverse Hybridisation Assay with conventional sequencing for determination of Hepatitis C Virus Genotype and Subtypes. Anti-HCV antibody was determined followed by HCV RNA extraction which was used for (1) viral load determination (2) qualitative real-time PCR RHA for genotyping and (3) conventional sequencing. Compared to conventional sequencing, accuracy of RHA results was 96.55% for determination of genotype (κ = 0.93) and 89.66% for subtype (κ = 0.85). Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of the qualitative PCR were 82.29%, 100%, 44.44% and 100% respectively with an accuracy of 86.84%. RHA is a less time consuming and cheaper method for determination of HCV genotype and subtype yet results must be interpreted with caution and quality control monitoring should be strictly followed to ensure validity.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-021-00729-9.
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http://dx.doi.org/10.1007/s13337-021-00729-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473521PMC
September 2021

Association of race and ethnicity with clinical phenotype, genetics, and survival in pediatric acute myeloid leukemia.

Blood Adv 2021 Oct 7. Epub 2021 Oct 7.

Baylor College of Medicine, Texas Children's Hospital, Houston, Texas, United States.

Black and Hispanic children with acute myeloid leukemia (AML) have worse outcomes compared to White children. AML is a heterogeneous disease with numerous genetic subtypes in which these disparities have not been specifically investigated. In this study, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to examine the association of race-ethnicity with leukemia cytogenetics, clinical features, and survival outcomes within major cytogenetic subgroups of pediatric AML. Compared to White non-Hispanic patients, t(8;21) AML was more prevalent among Black (OR, 2.22; 95% CI, 1.28-3.74) and Hispanic patients (OR, 1.74; 95% CI, 1.05-2.83). The poor prognosis KMT2A rearrangement t(6;11)(q27;q23) was more prevalent among Black patients (OR, 6.12; 95% CI, 1.81-21.59). Among those with KMT2Ar AML, Black race was associated with inferior event-free survival (EFS) (HR, 2.31; 95% CI, 1.41-3.79) and overall survival (OS) (HR, 2.54; 1.43-4.51). Hispanic patients with KMT2Ar AML also had inferior EFS (HR, 2.20; 95% CI, 1.27-3.80) and OS (HR, 2.07; 95% CI, 1.09-3.93). Similarly, among patients with t(8;21) or inv(16) AML (i.e., core binding factor AML), Black patients had inferior outcomes (EFS HR, 1.93; 95% CI, 1.14-3.28 and OS HR, 3.24; 95% CI, 1.60-6.57). This disparity was not detected among patients receiving gemtuzumab ozogamicin. In conclusion, racial-ethnic disparities in survival outcomes among young people with AML are prominent and vary across cytogenetic subclasses. Future studies should explore the socioeconomic and biologic determinants of these disparities.
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http://dx.doi.org/10.1182/bloodadvances.2021004735DOI Listing
October 2021

Utility of the ROX Index in Predicting Intubation for Patients With COVID-19-Related Hypoxemic Respiratory Failure Receiving High-Flow Nasal Therapy: Retrospective Cohort Study.

JMIRx Med 2021 Jul-Sep;2(3):e29062. Epub 2021 Aug 27.

Department of Thoracic Medicine and Surgery Temple University Hospital Philadelphia, PA United States.

Background: The use of high-flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concerns about increased health care worker transmission and delays in invasive mechanical ventilation (IMV). Herein, we analyzed the utility of the noninvasive ROX (ratio of oxygen saturation) index to predict the need for and timing of IMV.

Objective: This study aimed to assess whether the ROX index can be a useful score to predict intubation and IMV in patients receiving HFNT as treatment for COVID-19-related hypoxemic respiratory failure.

Methods: This is a retrospective cohort analysis of 129 consecutive patients with COVID-19 admitted to Temple University Hospital in Philadelphia, PA, from March 10, 2020, to May 17, 2020. This is a single-center study conducted in designated COVID-19 units (intensive care unit and other wards) at Temple University Hospital. Patients with moderate and severe hypoxemic respiratory failure treated with HFNT were included in the study. HFNT patients were divided into two groups: HFNT only and intubation (ie, patients who progressed from HFNT to IMV). The primary outcome was the value of the ROX index in predicting the need for IMV. Secondary outcomes were mortality, rate of intubation, length of stay, and rate of nosocomial infections in a cohort treated initially with HFNT.

Results: Of the 837 patients with COVID-19, 129 met the inclusion criteria. The mean age was 60.8 (SD 13.6) years, mean BMI was 32.6 (SD 8) kg/m², 58 (45%) were female, 72 (55.8%) were African American, 40 (31%) were Hispanic, and 48 (37.2%) were nonsmokers. The mean time to intubation was 2.5 (SD 3.3) days. An ROX index value of less than 5 at HFNT initiation was suggestive of progression to IMV (odds ratio [OR] 2.137, =.052). Any further decrease in ROX index value after HFNT initiation was predictive of intubation (OR 14.67, <.001). Mortality was 11.2% (n=10) in the HFNT-only group versus 47.5% (n=19) in the intubation group (<.001). Mortality and need for pulmonary vasodilators were higher in the intubation group.

Conclusions: The ROX index helps decide which patients need IMV and may limit eventual morbidity and mortality associated with the progression to IMV.
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http://dx.doi.org/10.2196/29062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404242PMC
August 2021

Astounding Fibro Lipoma of Spermatic Cord: A Diagnostic Dilemma.

Case Rep Surg 2021 4;2021:7139109. Epub 2021 Sep 4.

Department of General Surgery, All India Institute of Medical Sciences, Patna, India.

Background: Fibro lipoma of the spermatic cord is a very rare tumor with few cases reported in literature. Atypical presentation and site of swelling mystifies the diagnosis and creates bewildering situation intraoperatively. . A 30-year-old farmer presented with an elastic firm nonreducible, nontender swelling at inguinoscrotal region with positive cough impulse and history of laparoscopic inguinal hernia repair 3 years ago. Ultrasonography of the swelling revealed a heteroechoic lesion of size 7 × 6 centimeter with probable features of lipoma or desmoid. Fine needle aspiration drawn in consideration of the diagnostic dilemma reported a benign lipomatous swelling which on final histopathology turned out to be a fibro lipoma of size 7 × 6 × 5 cm.

Conclusion: Considering the age and presentation of the patient, it was astonishing. It provided an insight to the occurrence of fibro lipoma even in younger age group which in fact is the first case of its kind as per best of our knowledge. Malignancy should be ruled out in such cases, and complete excision is the treatment of choice.
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http://dx.doi.org/10.1155/2021/7139109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437671PMC
September 2021

Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities.

Blood Adv 2021 10;5(19):3876-3890

Department of Pediatrics, Baylor College of Medicine, and Texas Children's Hospital, Houston, TX.

IKAROS family zinc finger 1 (IKZF1) alterations represent a diverse group of genetic lesions that are associated with an increased risk of relapse in B-cell acute lymphoblastic leukemia. Due to the heterogeneity of concomitant lesions, it remains unclear how IKZF1 abnormalities directly affect cell function and therapy resistance, and whether their consideration as a prognostic indicator is valuable in improving outcome. CRISPR/Cas9 strategies were used to engineer multiple panels of isogeneic lymphoid leukemia cell lines with a spectrum of IKZF1 lesions to measure changes in chemosensitivity, gene expression, cell cycle, and in vivo engraftment that can be linked to loss of IKAROS protein. IKZF1 knockout and heterozygous null cells displayed relative resistance to a number of common therapies for B-cell acute lymphoblastic leukemia, including dexamethasone, asparaginase, and daunorubicin. Transcription profiling revealed a stem/myeloid cell-like phenotype and JAK/STAT upregulation after IKAROS loss. A CRISPR homology-directed repair strategy was also used to knock-in the dominant-negative IK6 isoform into the endogenous locus, and a similar drug resistance profile, with the exception of retained dexamethasone sensitivity, was observed. Interestingly, IKZF1 knockout and IK6 knock-in cells both have significantly increased sensitivity to cytarabine, likely owing to marked downregulation of SAMHD1 after IKZF1 knockout. Both types of IKZF1 lesions decreased the survival time of xenograft mice, with higher numbers of circulating blasts and increased organ infiltration. Given these findings, exact specification of IKZF1 status in patients may be a beneficial addition to risk stratification and could inform therapy.
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http://dx.doi.org/10.1182/bloodadvances.2020002408DOI Listing
October 2021

Multidisciplinary diagnosis of silicone granuloma-associated gluteal inflammation: Combined clinical, radiological and histopathological assessment.

Australas J Dermatol 2021 Aug 31. Epub 2021 Aug 31.

Department of Dermatology, Loma Linda University, Loma Linda, California, USA.

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http://dx.doi.org/10.1111/ajd.13706DOI Listing
August 2021

Riociguat for Sarcoidosis-Associated Pulmonary Hypertension: Results of a 1-Year Double-Blind, Placebo-Controlled Trial.

Chest 2021 Aug 4. Epub 2021 Aug 4.

Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, VA.

Background: Riociguat is effective in delaying the time to clinical worsening (TCW) in patients with groups 1 and 4 pulmonary hypertension.

Research Question: Is riociguat more effective than placebo in prolonging TCW in sarcoidosis-associated pulmonary hypertension (SAPH)?

Study Design And Methods: This was a double-blind placebo-controlled trial. Patients with SAPH confirmed by right heart catheterization were randomized 1:1 to riociguat or placebo. Patients underwent 6-min walk distance (6MWD) and spirometry testing every 8 weeks. The primary end point was TCW, which was defined by the time to the first of the following: (1) all-cause mortality, (2) need for hospitalization because of worsening cardiopulmonary status attributable to progression of disease, (3) > 50 m decrease in the 6MWD test, or (4) worsening of World Health Organization functional class.

Results: A total of 16 patients were randomized to riociguat (n = 8) or placebo (n = 8). No difference was found in pulmonary artery mean, pulmonary vascular resistance, initial 6MWD, or FVC between the two groups. Five of eight patients who received placebo met TCW criteria, whereas none of the patients who received riociguat experienced a qualifying event. By log-rank analysis, patients who received riociguat were in the study for a significantly longer period (χ  = 6.259; P = .0124). The 6MWD decreased in the placebo group (median, -55.9 m; range, -176.8 to 60 m), but rose in the riociguat group (median, +42.7 m; range, -7.5 to +91.4 m; P = .0149), with a placebo-corrected difference of 94 m (P < .01). Four of eight patients who received riociguat, but only 1 of 8 patients who received placebo, showed a > 30-m improvement in 6MWD (P > .05). No significant adverse events associated with riociguat occurred.

Interpretation: Over the 1 year of the study, riociguat was effective in preventing clinical worsening and improving exercise capacity in patients with SAPH.

Trial Registry: ClinicalTrials.gov; No.: NCT02625558; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.07.2162DOI Listing
August 2021

Blowing off steam-Identifying bowel perforation after routine colonoscopy.

Clin Case Rep 2021 Jul 23;9(7):e04515. Epub 2021 Jul 23.

Division of Pulmonary/Critical Care Department of Internal Medicine Michigan State University at Hurley Medical Center Flint MI USA.

Colonoscopy is an effective procedure for colorectal cancer (CRC) screening. Perforation is a rare yet the most severe complication, identified by landmarks-double dolphin, triangle, or double-wall sign signifying air and intracolonic contents leaking into the peritoneal space. Prompt recognition and surgical intervention are imperative to avoid high mortality.
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http://dx.doi.org/10.1002/ccr3.4515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299273PMC
July 2021

Sarcoidosis: An FP's primer on an enigmatic disease.

J Fam Pract 2021 04;70(3):E4-E15

Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (Drs. Gupta, Patel, and Parth Rali); Department of Family Medicine, Barbara and Zucker School of Medicine at Hofstra/ Northwell - South Shore University Hospital, NY (Drs. Caceres and Mayur Rali).

Management includes ruling out alternate diagnoses, identifying occult/overt organ involvement, determining treatment, and recognizing worrisome features.
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http://dx.doi.org/10.12788/jfp.0177DOI Listing
April 2021

Diffuse hemorrhagic blistering and erosions on a 13-year-old boy.

Pediatr Dermatol 2021 05;38(3):e24-e25

Department of Dermatology, Baylor College of Medicine, Houston, TX, USA.

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http://dx.doi.org/10.1111/pde.14547DOI Listing
May 2021

Thrombotic Microangiopathy Increases the Risk of Chronic Kidney Disease but Not Overall Mortality in Long-term Transplant Survivors.

Transplant Cell Ther 2021 10 1;27(10):864.e1-864.e5. Epub 2021 Jul 1.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Division of Nephrology, Seattle Children's Hospital, Seattle, Washington; Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington.

Thrombotic microangiopathy (TMA) after allogeneic hematopoietic cell transplant (HCT) is associated with acute kidney injury (AKI) and increased mortality. The impact of TMA on chronic kidney disease (CKD) and long-term mortality among HCT survivors has not been fully examined. To assess the risk of CKD and mortality in HCT survivors with and without history of TMA, we conducted a retrospective cohort study among adult allogeneic HCT recipients who survived to at least 1 year post-transplantation. We examined the association between the history of TMA within 1 year and the onset of CKD longitudinally for 5 years with generalized estimating equation (GEE) while adjusting for other key confounders. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m using the CKD-EPI formula with outpatient creatinine values collected during the annual long-term follow-up unit follow-up visits. Kaplan Meier curves landmarked at 1 year were used for survival analyses. Among 2091 adult patients who underwent allogeneic HCT, we identified 1151 patients who survived at least 1 year and had available long-term follow-up data. Among them, 57 patients developed TMA within 1 year and 1094 did not have TMA. There was no pretransplantation baseline difference in eGFR between groups. After adjusting for confounders, history of TMA was associated with an odds ratio of 2.83 (95% confidence interval 1.33-6.03) for CKD development over 5 years after transplantation. The conditional 5-year survival was 78% in the TMA survivors and 80% in the non-TMA survivors (log rank P = .122). HCT survivors with a history of TMA had increased risk of CKD development. Although TMA was associated with high risk of mortality within 1 year after transplantation, long-term survival was comparable with non-TMA survivors. Future therapeutic interventions should focus on not only short-term mortality outcomes, but also short- and long-term kidney outcomes for HCT patients with TMA.
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http://dx.doi.org/10.1016/j.jtct.2021.06.027DOI Listing
October 2021

Reversible Photothermal Modulation of Electrical Activity of Excitable Cells using Polydopamine Nanoparticles.

Adv Mater 2021 Aug 3;33(32):e2008809. Epub 2021 Jul 3.

Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, MO, 63130, USA.

Advances in the design and synthesis of nanomaterials with desired biophysicochemical properties can be harnessed to develop non-invasive neuromodulation technologies. Here, the reversible modulation of the electrical activity of neurons and cardiomyocytes is demonstrated using polydopamine (PDA) nanoparticles as photothermal nanotransducers. In addition to their broad light absorption and excellent photothermal activity, PDA nanoparticles are highly biocompatible and biodegradable, making them excellent candidates for both in vitro and in vivo applications. The modulation of the activity (i.e., spike rate of the neurons and beating rate of cardiomyocytes) of excitable cells can be finely controlled by varying the excitation power density and irradiation duration. Under optimal conditions, reversible suppression (≈100%) of neural activity and reversible enhancement (two-fold) in the beating rate of cardiomyocytes is demonstrated. To improve the ease of interfacing of photothermal transducers with these excitable cells and enable spatial localization of the photothermal stimulus, a collagen/PDA nanoparticle foam is realized, which can be used as an "add-on patch" for photothermal stimulation. The non-genetic optical neuromodulation approach using biocompatible and biodegradable nanoparticles represents a minimally invasive method for controlling the activity of excitable cells with potential applications in nano-neuroscience and engineering.
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http://dx.doi.org/10.1002/adma.202008809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363531PMC
August 2021

Genotypic distribution of hepatitis C virus in Uttarakhand.

Indian J Med Microbiol 2021 Oct-Dec;39(4):479-483. Epub 2021 Jun 29.

Dept. of Microbiology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India. Electronic address:

Purpose: Hepatitis C virus is a major cause of chronic hepatitis with seven known genotypes. Uttarakhand is a north Indian state in the Sub-Himalayan region where the genotypic distribution of HCV is largely unknown. This study was undertaken in order to assess the pattern of genotype and subtype and understand the risk factors leading to transmission of Hepatitis C virus in this understudied region.

Methods: Anti-HCV reactive cases were selected for determination of the circulating genotypes. Viral RNA was confirmed by real-time PCR. Strains were amplified and sequenced using Sanger's methods. Phylogenetic tree was constructed to determine the genotype.

Results: Genotype 3 was found to be the predominant genotype majority being subtype 3a and 3b followed by genotype 1. Subtypes 3g and genotype 4a were also observed. Major risk factor found was parenteral injection therapy from unregistered medical practitioners for minor ailments.

Conclusions: Findings of our study will help in tailoring management and prevention protocols for HCV for the people of this region.
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http://dx.doi.org/10.1016/j.ijmmb.2021.06.009DOI Listing
June 2021

COVID-19 Vaccines in Patients With Chronic Liver Disease.

J Clin Exp Hepatol 2021 Nov-Dec;11(6):720-726. Epub 2021 Jun 19.

Department of Gastroenterology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India.

The COVID-19 pandemic has caused mayhem globally since the beginning of 2020. Owing to the immune dysfunction inherent to cirrhosis and the poor general condition, patients with chronic liver disease (CLD) are at higher risk of mortality and morbidity due to COVID-19. Recently, a number of vaccines against SARS-Cov-2 have been approved for emergency use around the globe. Although the phase 2/3 trials of these vaccines show them to be safe and effective in the general population, data in patients with CLD are scarce. The number of patients with CLD enrolled on these trials is small, and no liver-related adverse effects have been reported yet. Various liver societies have come up with guidelines on vaccination in this population and recommend vaccination on a priority basis. Trials to assess the safety and efficacy of the COVID vaccines are underway and are likely to provide valuable insight into this matter.
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http://dx.doi.org/10.1016/j.jceh.2021.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214314PMC
June 2021

Splenic Injury After a Colonoscopy: Threading the Scope Carefully in Heritable Connective Tissue Disorders.

Cureus 2021 Jun 4;13(6):e15444. Epub 2021 Jun 4.

Gastroenterology and Hepatology, Ascension Genesys Hospital, Grand Blanc, USA.

Colonoscopies have reduced colorectal cancer (CRC) burden in the United States, and their utility has expanded to include various diagnostic and therapeutic indications. Complications are seen in up to 1% and increase with age and polypectomy. As colonoscopies become widespread, specific populations seem to be at a much higher risk; notably patients with heritable connective tissue disorders (HCTD). As life expectancy increases, these patients undergo routine screenings and require careful peri-endoscopic care to reduce adverse outcomes. Amongst HCTD, Ehlers-Danlos syndrome (EDS) is commonly implicated, however, no reports of Marfan syndrome (MS) exist. We present a unique case of splenic injury after colonoscopy in a patient with MS. Successful outcomes require early suspicion and emergent surgical evaluation in patients with hemodynamic instability after a colonoscopy. Increased ligament laxity and bowel fragility are the most likely mechanisms. Alternative CRC strategies like fecal immunochemical test (FIT), fecal occult, Cologuard, or virtual colonography can be considered.
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http://dx.doi.org/10.7759/cureus.15444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184110PMC
June 2021

The Patient's Perspective in Cirrhosis: Unmet Supportive Care Needs Differ by Disease Severity, Etiology, and Age.

Hepatol Commun 2021 May 6;5(5):891-905. Epub 2021 Feb 6.

Department of Gastroenterology and Hepatology Princess Alexandra Hospital Brisbane QLD Australia.

Patients with cirrhosis have significant physical, psychological, and practical needs. We documented patients' perceived need for support with these issues and the differences with increasing liver disease severity, etiology, and age. Using the supportive needs assessment tool for cirrhosis (SNAC), we examined the rate of moderate-to-high unmet needs (Poisson regression; incidence rate ratio [IRR]) and the correlation between needs and sociodemographic/clinical characteristics (multivariable linear regression) in 458 Australians adults with cirrhosis. Primary liver disease etiology was alcohol in 37.6% of patients, chronic viral hepatitis C in 25.5%, and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in 23.8%. A total of 64.6% of patients had Child-Pugh class A cirrhosis. Most patients (81.2%) had at least one moderate-to-high unmet need item; more than 25% reported a moderate-to-high need for help with "lack of energy," "sleep poorly," "feel unwell," "worry about … illness getting worse (liver cancer)," "have anxiety/stress," and "difficulty with daily tasks." Adjusting for key sociodemographic/clinical factors, patients with Child-Pugh C had a greater rate of "practical and physical needs" (vs. Child-Pugh A; IRR = 2.94, 95% confidence interval [CI] 2.57-3.37), patients with NAFLD/NASH had a greater rate of needs with "lifestyle changes" (vs. alcohol; IRR = 1.81, 95% CI 1.18-2.77) and "practical and physical needs" (IRR = 1.43, 95% CI 1.23-1.65), and patients aged ≥65 years had fewer needs overall (vs. 18-64 years; IRR = 0.70, 95% CI 0.64-0.76). Higher overall SNAC scores were associated with Child-Pugh B and C (both  < 0.001), NAFLD/NASH ( = 0.028), patients with "no partner, do not live alone" ( = 0.004), unemployment ( = 0.039), ascites ( = 0.022), and dyslipidemia ( = 0.024) compared with their counterparts. Very high levels of needs were reported by patients with cirrhosis. This information is important to tailor patient-centered care and facilitate timely interventions or referral to support services.
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http://dx.doi.org/10.1002/hep4.1681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122374PMC
May 2021

Evaluating the Impact of Provider Type and Patient Diagnosis on Patient No-Shows to Vascular Clinic.

WMJ 2021 Apr;120(1):41-44

Department of Surgery, Michael E. DeBakey VA Medical Center, Houston, Texas.

Background: No-shows are a source of burden that lead to wasted resources. While prior research has established that many patient-level affect impact no-show rates, the impact of referring provider-level factors, in particular the type of referring provider-and specific diagnosis are still largely unknown.

Materials And Methods: Retrospective chart review examining new patient consults scheduled for outpatient vascular surgery clinic from August 1, 2014 through February 28, 2015 was conducted. The specialty types of the referring physicians and the reason for referral (patient diagnosis) were recorded.

Results: Of 227 new patient consults scheduled, 30% were no-shows to their appointment. No-show rates were significantly higher when the patient was referred by a primary care physician versus a specialist and differed significantly based on patient diagnosis.

Conclusions: Given that referring provider type and patient diagnosis significantly affect noshow rates, interventions that integrate the community of providers are needed to reduce noshows.
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April 2021
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