Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes – A systematic review and meta-analysis

AimsThe effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders.MethodsWe conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis.ResultsGLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05–1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00–1.43), using placebo as a comparator (1.22, 1.05–1.42). In subgroups with patients who had T2DM ≥10 years (1.19, 0.99–1.42) or with subjects enrolled from multiple countries (1.2, 0.99–1.46), the association appeared to be evident but did not reach statistical significance.ConclusionsGLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted.     

Novel pathogenic variants in an Indian cohort with epidermolysis bullosa: Expanding the genotypic spectrum

BackgroundEpidermolysis bullosa (EB) is a genodermatosis characterized by skin fragility and blisters with variable severity. Patients with Dystrophic EB (DEB) or Junctional EB (JEB) mainly present to clinic due to greater functional impairment. Pathogenic sequence variations in COL7A1 are implicated in DEB.ObjectiveWe have tried to decipher the molecular spectrum and genotype phenotype correlation of 21 Indian patients with EB.MethodsNext generation sequencing (NGS) was performed to determine the pathogenic variants. Sanger sequencing was also done for validation of the variants in eleven individuals.ResultsPathogenic variants were detected in 20 individuals (diagnostic yield of 95%). Majority of them (90%) had sequence variation in COL7A1 while two had pathogenic variants in ITGB4 and KRT14 respectively. Out of the 18 patients confirmed to have DEB, 3 had Dominant DEB (DDEB) whereas 15 patients had Recessive DEB (RDEB). Amongst 23 sequence variations identified, 12 were found to be novel (3 were missense, 5 were premature termination codon variants while 4 were splice-site changes).ConclusionGenotype phenotype correlation was noted with milder manifestations in those with dominant inheritance types. Exact molecular diagnosis can be ascertained by NGS in majority of cases.     

Thyroid Embolization for Nonsurgical Treatment of Nodular Goiter: A Single-Center Experience in 56 Consecutive Patients

PurposeTo investigate the safety and efficacy of thyroid artery embolization (TAE) in the treatment of nodular goiter (NG).MethodsDuring a 5.5-year period, 56 consecutive patients with a NG underwent TAE. In Group A, there were 20 patients with a solitary/dominant 5–11-cm nodule, and in Group B, there were 36 patients with numerous nodules. Of the 56 patients, 47 (84%) had a retrosternal goiter and 25 had hyperthyroidism. In all patients, clinical and radiological evaluations were made at baseline and 6 months after TAE, and these parameters were statistically compared.ResultsIn 56 patients, 145 of the 146 thyroid arteries were successfully embolized. The 30-day mortality rate was 1.8%. Minor and major complications occurred in 25 and 2 patients, respectively. Six months after the TAE, the mean nodule volume was reduced from 80.2 mL to 25.0 mL, the mean thyroid volume was reduced from 147.0 mL to 62.6 mL, and the mean intrathoracic extension was reduced from 31.7 mm to 15.9 mm (P < .001). Of the 22 patients with non–Graves hyperthyroidism, 19 (86%) became euthyroid. The mean thyroid-related patient-reported outcome scores improved from 155.4 to 70.4 (P < .001). Of the 51 patients, 50 (98%) declared that they would recommend TAE to other patients with NG.ConclusionsTAE is safe and effective for the treatment of NG, with a significant volume reduction of the nodule(s) and thyroid gland.     

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

Vacuum myofascial therapy device for non-specific neck pain. A single blind randomized clinical trial

ObjectivesThis study aimed to investigate the efficacy of a vacuum myofascial therapy device (VT) for improving pressure pain thresholds (PPTs), range of motion (ROM), neck pain-related disability, pain, and quality of life in patients with non-specific neck pain.MethodsA randomized controlled trial in which thirty-eight participants with non-specific neck pain (NP) were randomly assigned to either an experimental (VT) or a comparison physical therapy program (PTP) group. The VT group (n = 19) received five sessions of treatment with a vacuum myofascial therapy device while the PTP group (n = 19) received five sessions of massage, ultrasound therapy (US), and transcutaneous electric nerve stimulation (TENS) over two weeks. The outcome measures were the numerical pain rating scale (NPRS), range of motion, quality of life (SF-12), neck disability Index (NDI), and PPTs at the end of treatment and at one-month follow-up.ResultsAlthough both groups experienced improvements in pain, neck disability, range of motion, and pressure pain, these only were statistically significant in the VT group. At one-month follow-up, the VT group still showed improvements in pain, neck disability, and range of motion.DiscussionVacuum myofascial therapy applied with a device offers similar results to other vacuum-based techniques such as cupping therapy. Moreover, in this device the parameters are digitally controlled, which allows for the precise reproduction of treatment.     

A Clinical and Economic Evaluation of Endoscopic Ultrasound for Patients at Risk for Familial Pancreatic Adenocarcinoma

Background and Aims: Approximately 10% of pancreatic adenocarcinoma is familial. Approximately 50% of Ist-degree relatives (FDRs) have endoscopic ultrasound (EUS) findings of chronic pancreatitis. We modeled the natural history of these patients to compare 4 management strategies. Methods: We performed a systematic review, and created a Markov model for 45-year-old male FDRs, with findings of chronic pancreatitis on screening EUS. We compared 4 strategies: doing nothing, prophylactic total pancreatectomy (PTP), annual surveillance by EUS, and annual surveillance with EUS and fine needle aspiration (EUS/FNA). Outcomes incorporated mortality, quality of life, procedural complications, and costs. Results: In the Do Nothing strategy, the lifetime risk of cancer was 20%. Doing nothing provided the greatest remaining years of life, the lowest cost, and the greatest remaining quality-adjusted life years (QALYs). PTP provided the fewest remaining years of life, and the fewest remaining QALYs. Screening with EUS provided nearly identical results to PTP, and screening with EUS/FNA provided intermediate results between PTP and doing nothing. PTP provided the longest life expectancy if the lifetime risk of pancreatic cancer was at least 46%, and provided the most QALYs if the risk was at least 68%. Conclusions: FDRs from familial pancreatic cancer kindreds, who have EUS findings of chronic pancreatitis, have increased risk for cancer, but their precise risk is unknown. Without the ability to further quantify that risk, the most effective strategy is to do nothing.     

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.