1.Predictive assessment with outcomes of phrenic nerve study in Guillain-Barré syndrome: a prospective study
Rajarshi CHAKRABORTY ; Rajesh VERMA ; Sarvesh Kumar CHAUDHARY ; Harish NIGAM ; Ankit KHETAN ; Swati SHAKYA ; Pushpita BARMAN ; Aparajita CHAKRABORTY
Journal of Yeungnam Medical Science 2025;42(1):45-
Background:
Guillain-Barré syndrome (GBS) is an acute acquired autoimmune inflammatory disorder of the peripheral nerves and roots. Respiratory insufficiency is an important predictor of a poor prognosis in patients with GBS. Phrenic nerve assessment is an area of interest in GBS with respiratory failure. We aimed to analyze the characteristics of the phrenic nerve conduction study (NCS) in GBS and assess its value in predicting respiratory failure requiring ventilatory support, along with outcome assessment at 6 months as per the Hughes score.
Methods:
A total of 135 patients with GBS admitted to our hospital over 3 years were thoroughly evaluated by clinical examination, blood laboratory tests, and phrenic NCS.
Results:
Phrenic NCS abnormality was observed in 48 patients (35.6%) with statistically significant increases in phrenic sum compound muscle action potential (CMAP) latency (18.91±7.82 ms) and sum CMAP duration (44.65±6.84 ms), along with reduced sum CMAP amplitude (0.3246±0.132 mV) and sum CMAP area (3.56±2.62 mV·ms) occurring in those requiring ventilatory assistance. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of the phrenic NCS for predicting respiratory failure in patients with GBS were 90.7%, 90.2%, 81.3%, 95.4%, 9.27, and 0.10, respectively. The results showed a statistically significant association between abnormal initial phrenic NCS scores and outcomes at 6 months.
Conclusion
Phrenic NCS can predict respiratory failure requiring ventilator assistance in patients with GBS. Phrenic NCS can be incorporated into routine NCS protocols to predict impending respiratory failure in patients with GBS.
3.Domperidone Exerts Antitumor Activity in Triple-Negative Breast Cancer Cells by Modulating Reactive Oxygen Species and JAK/STAT3 Signaling
Rajina SHAKYA ; Mi Ran BYUN ; Sang Hoon JOO ; Kyung-Soo CHUN ; Joon-Seok CHOI
Biomolecules & Therapeutics 2023;31(6):692-699
The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3.Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.
4.Incidence of Dural Tears in Open versus Minimally Invasive Spine Surgery: A Single-Center Prospective Study
Ayush SHARMA ; Akash SHAKYA ; Vijay SINGH ; Priyank DEEPAK ; Nilesh MANGALE ; Ajay JAISWAL ; Nandan MARATHE
Asian Spine Journal 2022;16(4):463-470
Methods:
This study included 420 operated cases of degenerative lumbar pathology with a prospective follow-up of at least 6 months. Patients were divided into the open surgery and MIS groups, and the incidences of DT, early return to work, and various demographic and operative factors were compared.
Results:
A total of 156 and 264 patients underwent MIS and open surgery, respectively. Incidental durotomy was documented in 52 cases (12.4%); this was significantly less in the MIS group versus the open surgery group (6.4% vs. 15.9%, p <0.05). In the open surgery group, four patients underwent revision for persistent dural leak or pseudomeningocele, but none of the cases in the MIS group had revision surgery due to DT-related complications. The incidence of DT was higher among patients with high body mass index, patients with diabetes mellitus, and patients who underwent revision surgery (p <0.05) regardless of the approach. The MIS group returned to work significantly earlier.
Conclusions
MIS was associated with a significantly lower incidence of DT and earlier return to work compared with open surgery among patients with degenerative lumbar pathology.
5.Hydroxyzine Induces Cell Death in Triple-Negative Breast Cancer Cells via Mitochondrial Superoxide and Modulation of Jak2/STAT3 Signaling
Rajina SHAKYA ; Gyu Hwan PARK ; Sang Hoon JOO ; Jung-Hyun SHIM ; Joon-Seok CHOI
Biomolecules & Therapeutics 2022;30(6):585-592
Treatment of triple-negative breast cancer (TNBC) has been limited due to the lack of molecular targets. In this study, we evaluated the cytotoxicity of hydroxyzine, a histamine H1 receptor antagonist in human triple-negative breast cancer BT-20 and HCC-70 cells. Hydroxyzine inhibited the growth of cells in dose- and time-dependent manners. The annexin V/propidium iodide double staining assay showed that hydroxyzine induced apoptosis. The hydroxyzine-induced apoptosis was accompanied down-regulation of cyclins and CDKs, as well as the generation of reactive oxygen species (ROS) without cell cycle arrest. The effect of hydroxyzine on the induction of ROS and apoptosis on TNBC cells was prevented by pre-treatment with ROS scavengers, N-acetyl cysteine or Mito-TEMPO, a mitochondria-targeted antioxidant, indicating that an increase in the generation of ROS mediated the apoptosis induced by hydroxyzine. Western blot analysis showed that hydroxyzine-induced apoptosis was through down-regulation of the phosphorylation of JAK2 and STAT3 by hydroxyzine treatment. In addition, hydroxyzine induced the phosphorylation of JNK and p38 MAPK. Our results indicate that hydroxyzine induced apoptosis via mitochondrial superoxide generation and the suppression of JAK2/STAT3 signaling.
6.The Great Imitator - Disseminated Tuberculosis Presenting as Baker’s Cyst: A Case Report
Shakya A ; Patil N ; Kakadiya G ; Soni Y
Malaysian Orthopaedic Journal 2022;16(No.1):126-129
Tuberculosis is known to be a great mimicker, and it can
present in a myriad of ways, which often result in an
incorrect diagnosis. In a country that is endemic to
tuberculosis, the presentation can take many forms ranging
from tumour to trauma. We present a case of Baker’s cyst
that was provisionally diagnosed as pigmented villonodular
synovitis (PVNS) of the knee and eventually turned out to be
tuberculous arthritis. A 46-year-old male presented with an
insidious swelling on the posterior aspect of his knee for one
year. Magnetic resonance imaging was suggestive of PVNS
as the likely diagnosis. The patient presented 21 days later
with a foot drop. On following-up with further
investigations, he was found to have a lesion at the level of
the L4-L5 spine. Chest radiograph changes were suggestive
of tuberculosis. A synovial biopsy of the knee was done, and
the tuberculosis culture report was positive. The patient was
started on anti-tubercular treatment and then operated on,
with arthroscopic synovectomy and posterior open cyst
excision. The histology report was positive for tuberculous
synovitis. The patient completed the course of antitubercular drugs and had physiotherapy. He demonstrated a
clinically and radiologically healed disease at the final
follow-up with a good functional outcome. Clinicians must
have a high index of suspicion for tuberculosis, especially in
endemic areas. Getting a chest radiograph is recommended
in every case. Early diagnosis with the appropriate treatment
will give a good functional outcome for the patient.
7.Diabetes Mellitus and the Development of Lumbar Canal Stenosis: Is There Any Relevance?
Ghanshyam KAKADIYA ; Kalpesh SAINDANE ; Yogesh SONI ; Kushal GOHIL ; Akash SHAKYA ; Mohhamad Umair ATTAR
Asian Spine Journal 2022;16(3):326-333
Methods:
LCS patients were divided into three groups as per DM status: group A without DM (n=150); group B patients with well-controlled DM; and group C patients with uncontrolled DM. Groups B and C were subdivided into group B1: patients with DM with a duration of ≤10 years (n=76), group B2: DM with duration of >10 years (n=68), group-C1 DM duration ≤10 years (n=56), and group C2 DM duration >10 years (n=48). The severity of LCS was evaluated using the Swiss Spinal Stenosis Scale (SSSS) and Modified Oswestry Disability score (MODS). Operated patients ligamentum flavum sent for histological staining and quantitative immunofluorescence analysis.
Results:
The demographic data of groups did not show any difference except in age. There was no difference between the mean SSSS and MODS of groups A and B1. Groups B2, C1, and C2 had higher average SSSS and MODS than group A (p<0.05). Groups B2 and C2 had higher SSSS and MODS than groups B1 and C1. Groups C1 and C2 had higher scores than groups B1 and B2 (p<0.05). The severity of LCS was significantly related to the duration of DM in groups B and C (p<0.05). Uncontrolled and longer duration of DM had significant elastin fibers loss and also higher rate of disk apoptosis, high matrix aggrecan fragmentation, and high disk glycosaminoglycan content.
Conclusions
Longer duration and uncontrolled diabetes were risk factors for LCS and directly correlate with the severity of LCS.
8.Mini suture anchor: An effective device for reduction and fixation of displaced temporomandibular joint disc with intracapsular condylar fracture.
Shubhechha SHAKYA ; Kai-De LI ; Dou HUANG ; Zuo-Qiang LIU ; Zhi-Ru LIU ; Lei LIU
Chinese Journal of Traumatology 2022;25(1):49-53
PURPOSE:
The main aim is to provide clinical reference for the application of mini suture anchor in the reduction and fixation of displaced temporomandibular joint (TMJ) disc with intracapsular condylar fracture.
METHODS:
From October 2018 to October 2019, 21 patients (31 sides) with intracapsular condylar fractures and articular disc displacement from West China Hospital of Stomatology, Sichuan University were included. The selection criteria were: (1) mandibular condylar fractures accompanied by displacement of the TMJ disc, confirmed by clinical examination, CT scan and other auxiliary examinations; (2) indication for surgical treatment; (3) no surgical contraindications; (4) no previous history of surgery in the operative area; (5) no facial nerve injury before the surgery; (6) informed consent to participate in the research program and (7) complete data. Patients without surgical treatment were excluded. The employed patients were followed up at 1, 3, 6 and 12 months after operation. Outcomes were assessed by success rate of operation, TMJ function and radiological examination results at 3 months after operation. Data were expressed as number and percent and analyzed using SPSS 19.0.
RESULTS:
All the surgical procedures were completed successfully and all the articular discs were firmly attached to the condyles. The articular disc sufficiently covered the condylar head after the fixation. The fixation remained stable when the mandible was moved in each direction by the surgeons. No complications occurred. The functions of the TMJ were well-recovered postoperatively in most cases. CT scan revealed that the screws were completely embedded in the bone without loosening or displacement.
CONCLUSION
Mini suture anchor can provide satisfactory stabilization for the reduced articular disc and also promote the recovery of TMJ functions.
Humans
;
Joint Dislocations/surgery*
;
Mandible
;
Mandibular Condyle
;
Mandibular Fractures/surgery*
;
Suture Anchors
;
Temporomandibular Joint Disc/surgery*
9.Virtual surgical planning is a useful tool in the surgical management of mandibular condylar fractures.
Shubhechha SHAKYA ; Kai-De LI ; Dou HUANG ; Zuo-Qiang LIU ; Xiao ZHANG ; Lei LIU
Chinese Journal of Traumatology 2022;25(3):151-155
PURPOSE:
The aim of this study is to evaluate the application value of virtual surgical planning in the management of mandibular condylar fractures and to provide a reliable reference.
METHODS:
This was a prospective randomized controlled study and recruited 50 patients requiring surgical treatment for their mandibular condylar fractures. The inclusion criteria were patients (1) diagnosed with a condylar fracture by two clinically experienced doctors and required surgical treatment; (2) have given consent for the surgical treatment; and (3) had no contraindications to the surgery. Patients were excluded from this study if: (1) they were diagnosed with a non-dislocated or only slightly dislocated condylar fracture; (2) the comminuted condylar fracture was too severe to be treated with internal reduction and fixation; or (3) patients could not complete follow-up for 3 months. There were 33 male and 17 female patients with 33 unilateral condylar fractures and 17 bilateral condylar fractures included. The 50 patients were randomly (random number) divided into control group (25 patients with 35 sides of condylar fractures) and experimental group (25 patients with 32 sides of condylar fractures). Virtual surgical planning was used in the experimental group, but only clinical experience was used in the control group. The patients were followed up for 1, 3, 6 and 12 months after operation. Variables including the rate of perfect reduction by radiological analysis, the average distance of deviation between preoperative and postoperative CT measurements using Geomagic software and postoperative clinical examinations (e.g., mouth opening, occlusion) were investigated for outcome measurement. SPSS 19 was adopted for data analysis.
RESULTS:
The average operation time was 180.60 min in the experimental group and 223.2 min in the control group. One week postoperatively, CT images showed that the anatomic reduction rate was 90.63% (29/32) in the experimental group and 68.57% (24/35) in the control group, revealing significant difference (X2 = 4.919, p = 0.027). Geomagic comparative analysis revealed that the average distance of deviation was also much smaller in the experimental group than that in the control group (0.639 mm vs. 0.995 mm; t = 3.824, p < 0.001).
CONCLUSION
These findings suggest that virtual surgical planning can assist surgeons in surgical procedures, reduce operative time, and improve the anatomic reduction rate & accuracy, and thus of value in the diagnosis and treatment of condylar fractures.
Female
;
Fracture Fixation, Internal/methods*
;
Fractures, Comminuted
;
Humans
;
Male
;
Mandibular Condyle/surgery*
;
Mandibular Fractures/surgery*
;
Prospective Studies
;
Treatment Outcome
10.Comparative Ligandomic Analysis of Human Lung Epithelial Cells Exposed to PM2.5
Hong TIAN ; SHAKYA AKHALESH ; Feng WANG ; Dong Wei WU ; Wei LI
Biomedical and Environmental Sciences 2020;33(3):165-173
Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm (PM2.5) alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity.Methods Human A549 lung epithelial cells (LECs) were treated with or without PM2.5. Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity. Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM2.5-treated LECs. Results We found 143 ligands with increased binding to PM2.5-treated LECs and 404 ligands with decreased binding. Many other ligands showed no change in binding activity. For example, apolipoprotein E (ApoE), Notch2, and growth arrest-specific 6 (Gas6) represent ligands with increased, decreased, or unchanged binding activity, respectively. Both ApoE and Gas6 are phagocytosis ligands, suggesting that phagocytic receptors on LECs after stimulation with PM2.5 were differentially upregulated by PM2.5. Conclusion These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM2.5 in terms of regulating the expression of cell surface receptors, as quantified by ligand binding activity. This quantitative ligandome profiling will provide in-depth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.


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