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Article: Rare Indication of Atlantoaxial Fusion-failed Conservative Management of Primary Atlantoaxial Osteoarthritis.

Dave, Bharat / Killekar, Rohan / Degulmadi, Devanand / Mayi, Shivanand / Rai, Ravi Ranjan / Dave, Mirant

2024 Volume 14, Issue 4, Page(s) 152–159

Abstract: Introduction: Osteoarthritis of the atlantoaxial joint is a significant cause of occipitocervical pain, which is often missed and has an increasing prevalence with age. The patients typically present with occipitocervical pain and restricted and painful ...

Abstract	Introduction: Osteoarthritis of the atlantoaxial joint is a significant cause of occipitocervical pain, which is often missed and has an increasing prevalence with age. The patients typically present with occipitocervical pain and restricted and painful neck rotations. Despite the primary reliance on conservative management for this pathology, surgical intervention becomes crucial for those not responding to standard conservative treatment. The presented case series highlights the rarity of the requirement of surgical intervention in the management of Atlantoaxial osteoarthritis (AAOA) and the clinical outcomes of surgical management in AAOA. Case report: This paper presents a case series of four patients who were managed surgically with atlantoaxial fusion, from a database of 108 patients with AAOA. The case series includes three males and one female with a mean age of presentation being 67.5 years. All four patients presented with occipitocervical pain, and painful neck movements and were diagnosed with AAOA on the anteroposterior open mouth view radiographs showing changes of osteoarthritis such as bone erosions, sclerosis, osteophytes. The patients were managed conservatively with non-steroidal anti-inflammatory drugs, intra-articular steroid injections, and cervical collar immobilization. Those not responding to conservative management and with incapacitating pain were managed surgically with atlantoaxial fusion procedures. Conclusion: In a group of patients with a painful and debilitating degenerative AAOA only a small proportion of cases require surgical intervention. In this cohort, only 3.70 % of patients required surgery, highlighting the rarity of surgical intervention required in the management of AAOA. Nevertheless, when conducted, atlantoaxial fusion has proved to be efficacious with a low rate of serious complications and the patient self-rated outcome in terms of post-operative visual analog scale score and neck disability index scores indicating a high degree of satisfaction with the procedures.
Language	English
Publishing date	2024-04-12
Publishing country	India
Document type	Case Reports
ZDB-ID	2658169-3
ISSN	2250-0685
ISSN	2250-0685
DOI	10.13107/jocr.2024.v14.i04.4394
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Article ; Online: Intestinal Barrier Dysfunction in Fatty Liver Disease: Roles of Microbiota, Mucosal Immune System, and Bile Acids.

Gupta, Biki / Rai, Ravi / Oertel, Michael / Raeman, Reben

Seminars in liver disease

2022 Volume 42, Issue 2, Page(s) 122–137

Abstract: Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of progressive liver diseases ranging from simple steatosis to steatohepatitis and fibrosis. Globally, NAFLD is the leading cause of morbidity and mortality associated with chronic liver ... ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of progressive liver diseases ranging from simple steatosis to steatohepatitis and fibrosis. Globally, NAFLD is the leading cause of morbidity and mortality associated with chronic liver disease, and NAFLD patients are at a higher risk of developing cirrhosis and hepatocellular carcinoma. While there is a consensus that inflammation plays a key role in promoting NAFLD progression, the underlying mechanisms are not well understood. Recent clinical and experimental evidence suggest that increased hepatic translocation of gut microbial antigens, secondary to diet-induced impairment of the intestinal barrier may be important in driving hepatic inflammation in NAFLD. Here, we briefly review various endogenous and exogenous factors influencing the intestinal barrier and present recent advances in our understanding of cellular and molecular mechanisms underlying intestinal barrier dysfunction in NAFLD.
MeSH term(s)	Bile Acids and Salts ; Gastrointestinal Microbiome ; Humans ; Immune System/pathology ; Inflammation ; Liver/pathology ; Liver Neoplasms/pathology ; Microbiota ; Non-alcoholic Fatty Liver Disease
Chemical Substances	Bile Acids and Salts
Language	English
Publishing date	2022-06-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603177-8
ISSN	1098-8971 ; 0272-8087
ISSN (online)	1098-8971
ISSN	0272-8087
DOI	10.1055/s-0042-1748037
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Article ; Online: Antagonizing Activin A/p15

Mekala, Sowmya / Rai, Ravi / Reed, Samantha Loretta / Bowen, Bill / Michalopoulos, George K / Locker, Joseph / Raeman, Reben / Oertel, Michael

Cells

2024 Volume 13, Issue 7

Abstract: Background/aim: Activin A is involved in the pathogenesis of human liver diseases, but its therapeutic targeting is not fully explored. Here, we tested the effect of novel, highly specific small-molecule-based activin A antagonists (NUCC-474/555) in ... ...

Abstract	Background/aim: Activin A is involved in the pathogenesis of human liver diseases, but its therapeutic targeting is not fully explored. Here, we tested the effect of novel, highly specific small-molecule-based activin A antagonists (NUCC-474/555) in improving liver regeneration following partial hepatectomy and halting fibrosis progression in models of chronic liver diseases (CLDs). Methods: Cell toxicity of antagonists was determined in rat hepatocytes and Huh-7 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay. Hepatocytes and hepatic stellate cells (HSCs) were treated with activin A and NUCC-555 and analyzed by reverse transcription-polymerase chain reaction and immunohistochemistry. Partial hepatectomized Fisher (F)344 rats were treated with NUCC-555, and bromodeoxyuridine (BrdU) incorporation was determined at 18/24/36/120/240 h. NUCC-555 was administered into thioacetamide- or carbon tetrachloride-treated F344 rats or C57BL/6 mice, and the fibrosis progression was studied. Results: NUCC-474 showed higher cytotoxicity in cultured hepatic cells; therefore, NUCC-555 was used in subsequent studies. Activin A-stimulated overexpression of cell cycle-/senescence-related genes (e.g., Conclusions: Our studies demonstrate that activin A antagonist NUCC-555 promotes liver regeneration and halts fibrosis progression in CLD models, suggesting that blocking activin A signaling may represent a new approach to treating people with CLD.
MeSH term(s)	Animals ; Humans ; Mice ; Rats ; Activins ; Bromodeoxyuridine ; Fibrosis ; Liver Diseases/drug therapy ; Mice, Inbred C57BL ; Rats, Inbred F344 ; Signal Transduction/drug effects
Chemical Substances	activin A ; Activins (104625-48-1) ; Bromodeoxyuridine (G34N38R2N1)
Language	English
Publishing date	2024-04-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells13070649
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Article ; Online: Does MR Signal Intensity Change have Prognostic Value in Multilevel Cervical Myelopathy? A Single-Center, Prospective Study.

Dave, Bharat R / Krishnan, Ajay / Rai, Ravi Ranjan / Degulmadi, Devanand / Mayi, Shivanand / Patidar, Vikram

Neurology India

2023 Volume 71, Issue 2, Page(s) 285–290

Abstract: Background and objective: Neurological recovery in cervical myelopathy remains unpredictable. There is contradictory literature regarding the prognostic value of magnetic resonance imaging (MRI) in such cases. The objective of the present study is to ... ...

Abstract	Background and objective: Neurological recovery in cervical myelopathy remains unpredictable. There is contradictory literature regarding the prognostic value of magnetic resonance imaging (MRI) in such cases. The objective of the present study is to evaluate the morphological changes in the spinal cord in cervical spondylotic myelopathy and compare them with clinical outcome. Materials and methods: This is a single-center, prospective, observational study. All patients with multilevel (two or more levels) cervical spondylotic myelopathy undergoing anterior spine surgery were included in the study. Patient demographics and radiological findings were recorded. MRI was repeated immediately post-op and at 1-year follow-up. MRI classification system based on axial images was used to evaluate presurgery and postsurgery changes and correlate them with clinical information. Results: The study comprised 50 patients (40 males and 10 females) with a mean age of 59.5 years. Average duration of symptoms before surgery was 6.29 months. Thirty-four patients underwent two-level decompression, while 16 patients underwent more than two-level decompression. Average duration of follow-up was 26.82 months. Mean pre-op Nurick grade was 2.84, and mean recovery rate was 56.73. Most common pre-op MRI type was type 1. Analysis of data by logistic regression showed better recovery rate with lower age, lower pre-op Nurick grade, and lower pre-op MRI type. Conclusion: MR classification based on signal intensity changes in axial images have been found to correlate with recovery rate.
MeSH term(s)	Male ; Female ; Humans ; Middle Aged ; Prognosis ; Prospective Studies ; Decompression, Surgical ; Spinal Cord Diseases/diagnostic imaging ; Spinal Cord Diseases/surgery ; Spinal Cord Diseases/pathology ; Magnetic Resonance Imaging/methods ; Cervical Vertebrae/diagnostic imaging ; Cervical Vertebrae/surgery ; Cervical Vertebrae/pathology ; Spinal Osteophytosis/diagnosis ; Treatment Outcome ; Spinal Cord Compression/diagnostic imaging ; Spinal Cord Compression/surgery ; Spinal Cord Compression/pathology ; Spondylosis/diagnostic imaging ; Spondylosis/surgery
Language	English
Publishing date	2023-05-08
Publishing country	India
Document type	Observational Study ; Journal Article
ZDB-ID	415522-1
ISSN	1998-4022 ; 0028-3886
ISSN (online)	1998-4022
ISSN	0028-3886
DOI	10.4103/0028-3886.375382
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Article: Intestinal Barrier Dysfunction in Fatty Liver Disease: Roles of Microbiota, Mucosal Immune System, and Bile Acids

Gupta, Biki / Rai, Ravi / Oertel, Michael / Raeman, Reben

Seminars in Liver Disease

2022 Volume 42, Issue 02, Page(s) 122–137

Abstract	Nonalcoholic fatty liver disease (NAFLD) describes a spectrum of progressive liver diseases ranging from simple steatosis to steatohepatitis and fibrosis. Globally, NAFLD is the leading cause of morbidity and mortality associated with chronic liver disease, and NAFLD patients are at a higher risk of developing cirrhosis and hepatocellular carcinoma. While there is a consensus that inflammation plays a key role in promoting NAFLD progression, the underlying mechanisms are not well understood. Recent clinical and experimental evidence suggest that increased hepatic translocation of gut microbial antigens, secondary to diet-induced impairment of the intestinal barrier may be important in driving hepatic inflammation in NAFLD. Here, we briefly review various endogenous and exogenous factors influencing the intestinal barrier and present recent advances in our understanding of cellular and molecular mechanisms underlying intestinal barrier dysfunction in NAFLD.
Keywords	NAFLD ; NASH ; intestinal permeability ; leaky gut ; microbiome ; bile acids ; inflammation ; mucosal immune cells
Language	English
Publishing date	2022-05-01
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	603177-8
ISSN	1098-8971 ; 0272-8087
ISSN (online)	1098-8971
ISSN	0272-8087
DOI	10.1055/s-0042-1748037
Database	Thieme publisher's database

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Article ; Online: 'Higher the grade-smaller the pedicle': a study of pedicle dimensional variations in 100 cases of high grade lytic spondylolisthesis.

Degulmadi, Devanand / Dave, Bharat / Krishnan, Ajay / Rai, Ravi Ranjan / Mayi, Shivanand / Chintam, Chaitanya Reddy

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society

2022 Volume 32, Issue 2, Page(s) 455–461

Abstract: Purpose: To measure the pedicle dimensions in high grade lytic spondylolisthesis (HGL) and to classify them, which helps the spine surgeon in proper selection of pedicle screws.: Methods: A study of CT scans in 100 consecutive patients between Jan ... ...

Abstract	Purpose: To measure the pedicle dimensions in high grade lytic spondylolisthesis (HGL) and to classify them, which helps the spine surgeon in proper selection of pedicle screws. Methods: A study of CT scans in 100 consecutive patients between Jan 2017 and April 2021 diagnosed as single-level HGL on standing radiographs. Pedicle height (PH), Pedicle width (PW), Differential pedicle height (DPH), Screw length (SL) and Transverse pedicle angle (TPA) were measured and analyzed. PH and PW were classified into four grades as-grade A less than 5.0 mm, grade B between 5.0 and 6.0 mm, grade C between 6.0 and 7.0 mm, and grade D above 7.0 mm. Results: 5 males and 95 females with mean age of 49.1 years. PH in 44% lytic vertebra were grade A, B (less than 6 mm) and the rest 56% had grade C, D (greater than 6 mm). PH averaged 6.6 mm in grade 3 HGL, 5.61 mm in grade 4 HGL. Change in PW, SL and TPA was not statistically significant with regards to grade or level of listhesis. A total of 37 cases were noted to have DPH (25 cases had a difference < 2 mm and 12 had a difference > 2 mm). Conclusion: 44% of the PH in lytic vertebra was grade A and B (less than 6 mm) that stresses the importance of pre-op CT assessment and planning the appropriate screw dimensions. Change in PH was statistically significant with regards to the grade of listhesis (P-value < 0.01). Differential pedicle height also need to be looked for.
MeSH term(s)	Male ; Female ; Humans ; Middle Aged ; Spondylolisthesis/diagnostic imaging ; Spondylolisthesis/surgery ; Pedicle Screws ; Tomography, X-Ray Computed/methods ; Cervical Vertebrae/surgery ; Repressor Proteins
Chemical Substances	Repressor Proteins
Language	English
Publishing date	2022-06-29
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1115375-1
ISSN	1432-0932 ; 0940-6719
ISSN (online)	1432-0932
ISSN	0940-6719
DOI	10.1007/s00586-022-07277-w
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Article: Western diet dampens T regulatory cell function to fuel hepatic inflammation in nonalcoholic fatty liver disease.

Chaudhary, Sudrishti / Rai, Ravi / Pal, Pabitra B / Tedesco, Dana / Singhi, Aatur D / Monga, Satdarshan P / Grakoui, Arash / Iyer, Smita S / Raeman, Reben

bioRxiv : the preprint server for biology

2023

Abstract: Background and aims: The immunosuppressive T regulatory cells (Tregs) regulate immune responses and maintain immune homeostasis, yet their functions in nonalcoholic fatty liver disease (NAFLD) pathogenesis remains controversial.: Methods: Mice were ... ...

Abstract	Background and aims: The immunosuppressive T regulatory cells (Tregs) regulate immune responses and maintain immune homeostasis, yet their functions in nonalcoholic fatty liver disease (NAFLD) pathogenesis remains controversial. Methods: Mice were fed a normal diet (ND) or a western diet (WD) for 16 weeks to induce NAFLD. Diphtheria toxin injection to deplete Tregs in Foxp3 Results: WD triggered accumulation of adaptive immune cells, including Tregs and effector T cells, within the liver parenchyma. This pattern was also observed in NASH patients, where an increase in intrahepatic Tregs was noted. In the absence of adaptive immune cells in Rag1 KO mice, WD promoted accumulation of intrahepatic neutrophils and macrophages and exacerbated hepatic inflammation and fibrosis. Similarly, targeted Treg depletion exacerbated WD-induced hepatic inflammation and fibrosis. In Treg-depleted mice, hepatic injury was associated with increased accumulation of neutrophils, macrophages, and activated T cells within the liver. Conversely, induction of Tregs using recombinant IL2/αIL2 mAb cocktail reduced hepatic steatosis, inflammation, and fibrosis in WD-fed mice. Analysis of intrahepatic Tregs from WD-fed mice revealed a phenotypic signature of impaired Treg function in NAFLD. Conclusions: Our findings indicate that the liver microenvironment in NAFLD impairs ability of Tregs to suppress effector immune cell activation, thus perpetuating chronic inflammation and driving NAFLD progression. These data suggest that targeted approaches aimed at restoring Treg function may represent a potential therapeutic strategy for treating NAFLD. Lay summary: In this study, we elucidate the mechanisms contributing to the perpetuation of chronic hepatic inflammation in nonalcoholic fatty liver disease (NAFLD). We show that dietary sugar and fatty acids promote chronic hepatic inflammation in NAFLD by impairing immunosuppressive function of regulatory T cells. Finally, our preclinical data suggest that targeted approaches aimed at restoring T regulatory cell function have the potential to treat NAFLD.
Language	English
Publishing date	2023-03-25
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.23.533977
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Book ; Online: Bidding combinatorial games

Kant, Prem / Larsson, Urban / Rai, Ravi K. / Upasany, Akshay V.

2022

Abstract: Combinatorial Game Theory is a branch of mathematics and theoretical computer science that studies sequential 2-player games with perfect information. Normal play is the convention where a player who cannot move loses. Here, we generalize the classical ... ...

Abstract	Combinatorial Game Theory is a branch of mathematics and theoretical computer science that studies sequential 2-player games with perfect information. Normal play is the convention where a player who cannot move loses. Here, we generalize the classical alternating normal play to infinitely many game families, by means of discrete Richman auctions (Develin et al. 2010, Larsson et al. 2021, Lazarus et al. 1996). We generalize the notion of a perfect play outcome, and find an exact characterization of outcome feasibility. As a main result, we prove existence of a game form for each such outcome class; then we describe their lattice structures. By imposing restrictions to the general families, such as impartial and {\em symmetric termination}, we find surprising analogies with alternating play. Comment: 5 figures
Keywords	Computer Science - Computer Science and Game Theory ; Mathematics - Combinatorics ; 91A46 ; 91A05
Publishing date	2022-07-17
Publishing country	us
Document type	Book ; Online
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Book ; Online: Constructive comparison in bidding combinatorial games

Kant, Prem / Larsson, Urban / Rai, Ravi K. / Upasany, Akshay V.

2022

Abstract: A class of discrete Bidding Combinatorial Games that generalize alternating normal play was introduced by Kant, Larsson, Rai, and Upasany (2022). The major questions concerning optimal outcomes were resolved. By generalizing standard game comparison ... ...

Abstract	A class of discrete Bidding Combinatorial Games that generalize alternating normal play was introduced by Kant, Larsson, Rai, and Upasany (2022). The major questions concerning optimal outcomes were resolved. By generalizing standard game comparison techniques from alternating normal play, we propose an algorithmic play-solution to the problem of game comparison for bidding games. We demonstrate some consequences of this result that generalize classical results in alternating play (from Winning Ways 1982 and On Numbers and Games 1976). In particular, integers, dyadics and numbers have many nice properties, such as group structures, but on the other hand the game * is non-invertible. We state a couple of thrilling conjectures and open problems for readers to dive into this promising path of bidding combinatorial games. Comment: 23 pages, 1 figure
Keywords	Computer Science - Computer Science and Game Theory ; Mathematics - Combinatorics ; 91A46 ; 91A05
Subject code	700
Publishing date	2022-07-23
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Limbus Vertebral Fracture Presenting as Cauda Equina Syndrome Masquerading An Acute Disc Prolapse - A Rare Case Report and Review of Literature.

Palliyil, Nigil Sadanandan / Rai, Ravi Ranjan / Deogaonkar, Kedar

Journal of orthopaedic case reports

2019 Volume 8, Issue 4, Page(s) 38–40

Abstract: Introduction: Limbus vertebral fracture is an uncommon injury described in adolescents. It refers to the separation of a bony fragment from the unfused ring apophysis of lumbar vertebral end plate. It usually presents with back pain with/without ... ...

Abstract	Introduction: Limbus vertebral fracture is an uncommon injury described in adolescents. It refers to the separation of a bony fragment from the unfused ring apophysis of lumbar vertebral end plate. It usually presents with back pain with/without radiculopathy masquerading an acute disc prolapse. However, the presentation as acute cauda equina syndrome has seldom been reported. Case report: A 15-year-old male presented to the casualty with a history of acute-onset low back pain and bilateral lower limb radicular pain with weakness, after lifting of a heavy Indian musical instrument (Dholak). This was associated with urinary retention and numbness in perineal region. Examination revealed L5 and S1 weakness with absent ankle jerks bilaterally. Bulbocavernosus reflex was absent. Emergency magnetic resonance imaging imaging was done, which revealed a limbus fracture of cephalad part of L4 vertebral body with displaced fragment into the spinal canal causing compression of the cauda equina. Emergency surgery was done in the form of L3-L4 midline interlaminar microscopic decompression. The patient had complete neurological recovery including the bladder control within 1 month of surgery. The patient had no functional deficits during follow-up at 3 and6 months. Dynamic radiographs taken at the end of 6 months did not show any sign of instability. Conclusion: When an adolescent patient with no previous history of backpain presents with acute cauda equina syndrome, a possibility of limbus fracture should also be considered. Early diagnosis and surgical decompression in such cases can bring about complete neurological recovery and excellent clinical outcome.
Language	English
Publishing date	2019-01-25
Publishing country	India
Document type	Case Reports
ZDB-ID	2658169-3
ISSN	2250-0685
ISSN	2250-0685
DOI	10.13107/jocr.2250-0685.1150
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