Publications by authors named "S Singh"

Background And Aims: Safety is a key consideration when choosing advanced therapies (biologic agents and oral small molecule inhibitors/modulators) in patients with inflammatory bowel diseases (IBD). We performed a systematic review and meta-analysis comparing the risk of serious infections with advanced therapies in active comparator studies.

Methods: Through a systematic search until February 28, 2022, we included 20 head-to-head studies comparing risk of serious infections with tumor necrosis factor (TNF)-α antagonists, vedolizumab, ustekinumab, tofacitinib, filgotinib and ozanimod in patients with IBD. We performed random effects meta-analysis comparing different advanced therapies.

Results: No significant difference was observed in the risk of serious infections between vedolizumab vs. TNFα antagonists in all patients with IBD (17 cohorts: OR, 0.84 [95% CI, 0.68-1.04]), with moderate heterogeneity (I=37%); on subgroup analysis, vedolizumab was associated with lower risk of serious infections in patients with ulcerative colitis (UC) (11 cohorts: OR, 0.68 [0.56-0.83], I=0%), but not in Crohn's disease (CD) (9 cohorts: OR, 1.03 [0.78-1.35], I=42%). Age, sex, prior biologic exposure and use of biologic monotherapy did not influence this association. In patients with CD, ustekinumab was associated with lower risk of serious infections vs. TNFα antagonists (3 cohorts: OR, 0.49 [0.25-0.93], I=16%) and vs. vedolizumab (3 cohorts: OR, 0.40 [0.17-0.93], I=67%). Few studies compared other advanced therapies.

Conclusions: Vedolizumab may offer net benefit over TNFα antagonists in patients with UC, but not in CD. Ustekinumab may offer net benefit over TNFα antagonists and vedolizumab in patients with CD.

Purpose: Vision and ergonomics are crucial variables for successful outcomes during neurosurgery procedures. Two-dimension video telescope operating monitor (VITOM) exoscope has emerged as an alternative, which is cheaper than microscope. The aim of this study is to evaluate the clinical utility of 2D VITOM and to compare its merits and demerits with respect to microscope.

Methods: VITOM 2D (Karl Storz, Germany) was used in 9 cranial and 5 spinal pediatric cases. While KINEVO operative microscope (Carl Zeiss, Germany) was used in 12 cranial and 6 spinal pediatric patients. All surgeries were performed by single senior neurosurgeon. The author's experience and opinions, as well as qualitative data, were analyzed. A comparison was made on image quality, illumination, field of view, and magnification of the operative field and ergonomics.

Results: Seven out of 9 cranial pediatric cases were switched from VITOM 2D to operative microscope due to low-image definition in depth of cranial cavity. Poor visualization of bleeding source in surgical field was another major drawback. Two cranial cases in which exoscope were used exclusively, included superficial tumors. In all 5 spinal cases, VITOM 2D was successfully used without any major difficulty. The exoscope's advantages were observed in ergonomics and ease in switching to naked eyes, but the microscope's field of view, illumination, magnification, and user-friendliness was considered superior.

Conclusion: 2D-VITOM is best suited for spinal and superficial cranial tumors. However, a lot of modifications are to be done especially in optics to become a substitute for operative microscope.

Background: Silibinin (SBN), a sirtuin 1 (SIRT1) activator, has been evaluated for its anti-inflammatory activity in many inflammatory diseases. However, its role in diabetes-induced peripheral neuropathy (DPN) remains unknown. The SIRT1 activation convalesces nerve functions by improving mitochondrial biogenesis and mitophagy.

Methods: DPN was induced by streptozotocin (STZ) at a dose of 55 mg/kg, i.p. in the male SD rats whereas neurotoxicity was induced in Neuro2A cells by 30 mM (high glucose) glucose. Neurobehavioural (nerve conduction velocity and nerve blood flow) western blot, immunohistochemistry, and immunocytochemistry were performed to evaluate the protein expression and their cellular localisation.

Results: Two-week SBN treatment improved neurobehavioural symptoms, SIRT1, PGC-1α, and TFAM expression in the sciatic nerve and HG insulted N2A cells. It has also maintained the mitophagy by up-regulating PARL, PINK1, PGAM5, LC3 level and provided antioxidant defence by upregulating Nrf2.

Conclusion: SBN has shown neuroprotective potential in DPN through SIRT1 activation and antioxidant mechanism.

Background And Aims: Sarcopenic obesity (SO) marks a confluence of 2 complex entities involving the muscle-liver-adipose tissue axis. Computed tomographic (CT) scan-derived skeletal muscle index (SMI) remains the gold standard for sarcopenia assessment in SO. However, it has intrinsic limitations of cost, radiation, and point of care applicability. We assessed the role of muscle ultrasound (US) in SO.

Methods: A total of 52 patients with cirrhosis and obesity were assessed for sarcopenia using SMI. US assessment of thigh and forearm muscles was done to record quadriceps muscle thickness (QMT), quadriceps feather index (QMFI), forearm muscle thickness (FMT), and forearm feather index (FFI), respectively. Evaluated US parameters were correlated with SMI and assessed for diagnostic accuracy using the area under the curve.

Results: A total of 40 (76.9%) males and 12 (23.1%) females [mean age: 50.9 y (43.8 to 53.5 y)] were included. QMT [0.45 cm/m2 (0.42 to 0.48 cm/m2) vs. 0.67 cm/m2 (0.63 to 0.70 cm/m2)], QMFI [0.82 cm/m2 (0.77 to 0.87 cm/m2) vs. 1.12 cm/m2 (1.06 to 1.19 cm/m2)], FMT [0.19 cm/m2 (0.17 to 0.20 cm/m2) vs. 0.25 cm/m2 (0.23 to 0.27 cm/m2)], and FFI [0.38 cm/m2 (0.35 to 0.412 cm/m2) vs. 0.47 cm/m2 (0.44 to 0.50 cm/m2)] were significantly lower in patients with SO (P<0.01). A positive correlation with SMI was seen for all parameters in the entire cohort. The strongest correlation was exhibited by QMT (r=0.70) and QMFI (r=0.70) in males. The area under the curve of QMT, QMFI, FMT, and FFI were 0.98 (95% confidence interval: 0.96-1), 0.95 (0.89-1), 0.85 (0.75-0.96), and 0.80 (0.68-0.93), respectively.

Conclusions: US-based assessment of sarcopenia has excellent diagnostic accuracy and correlates well with computed tomography-SMI in patients with SO. US may serve as an easy-to-use, point of care tool for assessing sarcopenia in SO with the advantage of repeated sequential assessment.

The various stressors in chronic unpredictable stress (CUS) triggers depressive behavior, impairs learning, and decision-making abilities. The present study investigated the effects of seed oil (CPSO) alone and in combination with fluoxetine (FLU) in modified CUS (mCUS) induced depression in mice. In this study, adult albino mice were subjected to a modified version of CUS protocol having six different stressors and were applied daily consistently for 15 days. The post-treatment with CPSO (50 and 100 mg/kg) and FLU (10 mg/kg) alone and in combination from day 16th to 36th. Group I: normal control; group II: diseased control (mCUS subjected group); group III: CPSO (50 mg/kg); group IV: CPSO (100 mg/kg); group V: CPSO (50 mg/kg)+FLU (10 mg/kg); group VI: CPSO (100 mg/kg)+FLU (10 mg/kg); group VII: FLU (10 mg/kg); group VIII: FLU (20 mg/kg). During experimentation, various behavioral, biochemical, oxidative stress, inflammatory, and neurotransmitters level were checked. The CUS treated mice exhibited increased escaped latency, decreased number of open arm entries, increased immobility time, decreased percentage of sucrose consumption, and number of the boxes crossed as compared to the normal group. The post-treatment with the CPSO 50 + FLU 10, CPSO 100 + FLU 10, FLU 10 significantly ( < 0.05) attenuated behavioral, biochemical, inflammation, corticosteroid, and neurotransmitters level as compared to CPSO 50, CPSO 100, and FLU 20 alone. CPSO along with FLU appreciably achieved anti-depressant effect via lowering stress, inflammation, corticosteroid level, and restoration of neurotransmitters level in mCUS induced depression mice model.