1.Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in children and young adults: a systematic review and meta-analysis
Lakshmi NAGENDRA ; Deep DUTTA ; Harish Bukkasagar GIRIJASHANKAR ; Deepak KHANDELWAL ; Tejal LATHIA ; Meha SHARMA
Annals of Pediatric Endocrinology & Metabolism 2024;29(2):82-89
Purpose:
Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap.
Methods:
Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events.
Results:
From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93–3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08–2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01–8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44–12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21–96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24–26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, β-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05–0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001).
Conclusion
SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.
3.Ruptured mirror DACA aneurysm: A rare case report and review of literature
Deepak Kumar SINGH ; Prevesh Kumar SHARMA ; Arun Kumar SINGH ; Vipin Kumar CHAND
Journal of Cerebrovascular and Endovascular Neurosurgery 2023;25(3):340-346
Bilateral distal anterior cerebral artery (DACA) aneurysms also called “kissing aneurysms” or “mirror aneurysm” are extremely rare, accounting for only 0.2% of all intracranial aneurysms. There have only been a few examples of mirror DACA aneurysms reported in the literature. Here, we report a rare case of mirror DACA aneurysm in a middle aged female with its successful clipping. Patient was admitted with severe headache and altered sensorium. Computed tomography (CT) head was suggestive of anterior inter-hemispheric hematoma. Digital subtraction angiography (DSA) was done which was suggestive of two distal anterior cerebral artery aneurysms located at same anatomical position. It was treated through microsurgical clipping. Mirror image DACA aneurysms are rare occurrence. All patients with ruptured DACA aneurysms should have angiography with 3D reconstruction studies. This aids in determining the aneurysm’s morphology and planning treatment accordingly.
4.Addition of computed tomography chest increases the diagnosis rate in patients with suspected intestinal tuberculosis
Saurabh KEDIA ; Raju SHARMA ; Sudheer Kumar VUYYURU ; Deepak MADHU ; Pabitra SAHU ; Bhaskar KANTE ; Prasenjit DAS ; Ankur GOYAL ; Karan MADAN ; Govind MAKHARIA ; Vineet AHUJA
Intestinal Research 2022;20(2):184-191
Background/Aims:
Intestinal tuberculosis (ITB) is difficult to diagnose due to poor sensitivity of definitive diagnostic tests. ITB may be associated with concomitant pulmonary tuberculosis (PTB) which may remain undetected on chest X-ray. We assessed the role of contrast enhanced computed tomography (CECT) chest in detecting the prevalence of active PTB, and increasing the diagnostic yield in patients with suspected ITB.
Methods:
Consecutive treatment naïve patients with suspected ITB (n=200) who underwent CECT chest (n=88) and had follow-up duration>1 year were recruited in this retrospective study (February 2016 to October 2018). ITB was diagnosed in the presence of caseating granuloma, positive acid fast stain or culture for Mycobacterium tuberculosis on biopsy, presence of necrotic lymph nodes (LNs) on CT enterography or positive response to anti-tubercular therapy. Evidence of active tuberculosis on CECT-chest was defined as presence of centrilobular nodules with or without consolidation/miliary nodules/thick-walled cavity/enlarged necrotic mediastinal LNs.
Results:
Sixty-five of eighty-eight patients (mean age, 33.8±12.8 years; 47.7% of females) were finally diagnosed as ITB (4-caseating granuloma on biopsy, 12-necrotic LNs on CT enterography, 1-both, and 48-response to anti-tubercular therapy) and 23 were diagnosed as Crohn’s disease. Findings of active TB on CECT chest with or without necrotic abdominal LNs were demonstrated in 5 and 20 patients, respectively. No patient with Crohn’s disease had necrotic abdominal LNs or active PTB. Addition of CECT chest in the diagnostic algorithm improved the sensitivity of ITB diagnosis from 26.2% to 56.9%.
Conclusions
Addition of CECT chest significantly improves the sensitivity for definite diagnosis in a patient with suspected ITB.
5.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.
6.Use of covered stent (CGuard) in the treatment of post-traumatic internal carotid artery pseudoaneurysm
Deepak SINGH ; Diwakar SHANKAR ; Gaurav SHARMA ; Kuldeep YADAV ; Mohammad KAIF
Journal of Cerebrovascular and Endovascular Neurosurgery 2022;24(3):257-262
Post-traumatic internal carotid artery pseudoaneurysm (ICA PSA) is a rare occurrence with high mortality rates, and with the advent of endovascular therapy, its treatment has shown drastic improvement in clinical as well as radiological outcomes. Here we are describing our experience with the CGuard embolic protection system (InspireMD, Tel Aviv, Israel) for the treatment of post-traumatic left ICA PSA in a 49-year-old male. New improved biomechanics and navigability have proven it to be a safe and efficient treatment modality for ICA PSA. However, a multicentric large-scale randomized trial is recommended to support this modality.
7.Conjoint Nerve Root an Intraoperative Challenge in Minimally Invasive Tubular Discectomy
Ayush SHARMA ; Vijay SINGH ; Romit AGRAWAL ; Nilesh MANGALE ; Priyank DEEPAK ; Jeet SAVLA ; Ajay JAISWAL
Asian Spine Journal 2021;15(4):545-549
Conjoint nerve root (CNR) is an embryological nerve root anomaly that mainly involves the lumbosacral region. The presence of CNR during tubular discectomy raises the chances of failure in spinal surgery and the risk of neural injuries. Tubular discectomy can be challenging in the presence of CNR owing to limited visualization. Here, we present a technical note on two cases of L5–S1 disc prolapse in the presence of conjoint S1 nerve root that was operated via a minimally invasive tubular approach. Any intraoperative suspicion of CNR while using the tubular approach should prompt the surgeon to perform a thorough tubular decompression prior to nerve root retraction. In patients with a large disc, disc should be approached via the axilla because the axillary area between the dura and the medial boarder of the root is very easy to approach in the presence of CNR. Safe performance of tubular discectomy is possible even in the presence of CNR in the lumbar spine.
8.A comparative study between light transmission aggregometry and flow cytometric platelet aggregation test for the identification of platelet function defects in patients with bleeding
Praveen SHARMA ; Man Updesh Singh SACHDEVA ; Narender KUMAR ; Sunil BOSE ; Parveen BOSE ; Varun UPPAL ; Pankaj MALHOTRA ; Deepak BANSAL ; Neelam VARMA ; Jasmina AHLUWALIA
Blood Research 2021;56(2):109-118
Background:
Platelet aggregation studies using conventional light transmission aggregometry (LTA) have several disadvantages and require strict pre-analytical measures for reliable results.We aimed to examine the utility of flow cytometric platelet aggregation (FCA) assay in detecting platelet function defects (PFDs) in patients with a history of bleeding symptoms.
Methods:
Sixty-four participants (24 patients and 40 healthy controls) were included in this study.LTA and FCA assay were performed simultaneously in patients and healthy controls. In the FCA assay, two portions of platelets from the same individual were labeled separately with CD31-FITC and CD31-PE. After mixing and stimulation with agonists, the double-colored platelet aggregates were visualized using a flow cytometer. The results generated using the two techniques were compared and correlated.
Results:
The patients’ median age was 17 years (range, 3‒72 yr) with a male-to-female ratio of 1:1.7. There was substantial agreement between LTA and FCA assay in detecting a PFD (κ=0.792). Four patients showing a Glanzmann thrombasthenia-like pattern on LTA exhibited an abnormal FCA. A functional defect in collagen binding was detected on the FCA assay conducted in two immune thrombocytopenic patients with severe bleeding.
Conclusion
FCA assay can be used to identify functional defects in platelets, with potential applications in thrombocytopenic individuals. It also facilitates the diagnosis of inherited bleeding disorders with platelet defects.
9.Efficacy and Safety of the Novel Dipeptidyl Peptidase-4 Inhibitor Gemigliptin in the Management of Type 2 Diabetes: A Meta-Analysis
Deep DUTTA ; Anshita AGARWAL ; Indira MAISNAM ; Rajiv SINGLA ; Deepak KHANDELWAL ; Meha SHARMA
Endocrinology and Metabolism 2021;36(2):374-387
Background:
No meta-analysis has holistically analysed and summarised the efficacy and safety of gemigliptin in type 2 diabetes. The meta-analysis addresses this knowledge gap.
Methods:
Electronic databases were searched for randomised controlled trials (RCTs) involving diabetes patients receiving gemigliptin in the intervention arm and placebo/active comparator in the control arm. The primary outcome was change in haemoglobin A1c (HbA1c). The secondary outcomes were alterations in glucose, glycaemic targets, lipids, insulin resistance, and adverse events.
Results:
Data from 10 RCTs involving 1,792 patients were analysed. Four had an active control group (ACG), with metformin/dapagliflozin/sitagliptin/glimepiride as the active comparator; six had a passive control group (PCG), with placebo/rosuvastatin as controls. HbA1c reduction by gemigliptin at 24 weeks was comparable to ACG (mean difference [MD], 0.09%; 95% confidence interval [CI], –0.06 to 0.23; P=0.24; I2=0%; moderate certainty of evidence [MCE]), but superior to PCG (MD, –0.91%; 95% CI, –1.18 to –0.63); P<0.01; I2=89%; high certainty of evidence [HCE]). Gemigliptin was superior to PCG regarding achieving HbA1c <7% (12 weeks: odds ratio [OR], 5.91; 95% CI, 1.34 to 26.08; P=0.02; I2=74%; 24 weeks: OR, 4.48; 95% CI, 2.09 to 9.60; P<0.01; I2=69%; HCE). Gemigliptin was comparable to ACG regarding achieving HbA1c <7% after 24 weeks (OR, 0.92; 95% CI, 0.52 to 1.63; P=0.77; I2=66%; MCE). Adverse events were similar between the gemigliptin and control groups (risk ratio [RR], 1.06; 95% CI, 0.82 to 1.36; P=0.66; I2=35%; HCE). The gemigliptin group did not have increased hypoglycaemia (RR, 1.19; 95% CI, 0.62 to 2.28; P=0.61; I2=19%; HCE).
Conclusion
Gemigliptin has good glycaemic efficacy and is well-tolerated over 6 months of use.
10.Conjoint Nerve Root an Intraoperative Challenge in Minimally Invasive Tubular Discectomy
Ayush SHARMA ; Vijay SINGH ; Romit AGRAWAL ; Nilesh MANGALE ; Priyank DEEPAK ; Jeet SAVLA ; Ajay JAISWAL
Asian Spine Journal 2021;15(4):545-549
Conjoint nerve root (CNR) is an embryological nerve root anomaly that mainly involves the lumbosacral region. The presence of CNR during tubular discectomy raises the chances of failure in spinal surgery and the risk of neural injuries. Tubular discectomy can be challenging in the presence of CNR owing to limited visualization. Here, we present a technical note on two cases of L5–S1 disc prolapse in the presence of conjoint S1 nerve root that was operated via a minimally invasive tubular approach. Any intraoperative suspicion of CNR while using the tubular approach should prompt the surgeon to perform a thorough tubular decompression prior to nerve root retraction. In patients with a large disc, disc should be approached via the axilla because the axillary area between the dura and the medial boarder of the root is very easy to approach in the presence of CNR. Safe performance of tubular discectomy is possible even in the presence of CNR in the lumbar spine.

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