Nevin Manimala

EJNMMI Res. 2022 May 7;12(1):28. doi: 10.1186/s13550-022-00900-3.

ABSTRACT

BACKGROUND: Although most guidelines suggest performing a positron emission tomography/computed tomography (PET/CT) with somatostatin receptor (SSTR) ligands for staging of pulmonary carcinoid tumours (PC), only a limited number of studies have evaluated the role of this imaging tool in this specific patient population. The preoperative differentiation between typical carcinoid (TC) and atypical carcinoid (AC) and the extent of dissemination (N/M status) are crucial factors for treatment allocation and prognosis of these patients. Therefore, we performed a pathology-based retrospective analysis of the value of SSTR PET/CT in tumour grading and detection of nodal and metastatic involvement of PC and compared this with the previous literature and with [¹⁸F]FDG PET/CT in a subgroup of patients.

METHODS: SSTR PET/CT scans performed between January 2007 and May 2020 in the context of PC were included. If available, [¹⁸F]FDG PET/CT images were also evaluated. The maximum standardized uptake (SUV_max) values of the primary tumour, of the pathologically examined hilar and mediastinal lymph node stations, as well as of the distant metastases, were recorded. Tumoural SUV_max values were related to the tumour type (TC versus AC) for both SSTR and [¹⁸F]FDG PET/CT in diagnosing and differentiating both tumour types. Nodal SUV_max values were compared to the pathological status (N⁺ versus N^–) to evaluate the diagnostic accuracy of SSTR PET/CT in detecting lymph node involvement. Finally, a mixed model analysis of all pathologically proven distant metastatic lesions was performed.

RESULTS: A total of 86 SSTR PET/CT scans performed in 86 patients with PC were retrospectively analysed. [¹⁸F]FDG PET/CT was available in 46 patients. Analysis of the SUV_max values in the primary tumour showed significantly higher SSTR uptake in TC compared with AC (median SUV_max 18.4 vs 3.8; p = 0.003) and significantly higher [¹⁸F]FDG uptake in AC compared to TC (median SUV_max 5.4 vs 3.5; p = 0.038). Receiver operating characteristic (ROC) curve analysis resulted in an area under the curve (AUC) of 0.78 for the detection of TC on SSTR PET/CT and of 0.73 for the detection of AC on [¹⁸F]FDG PET/CT. A total of 267 pathologically evaluated hilar and mediastinal lymph node stations were analysed. ROC analysis of paired SSTR/[¹⁸F]FDG SUV_max values for the detection of metastasis of TC in 83 lymph node stations revealed an AUC of 0.91 for SSTR PET/CT and of 0.74 for [¹⁸F]FDG PET/CT (difference 0.17; 95% confidence interval – 0.03 to 0.38; p = 0.10). In a sub-cohort of 10 patients with 12 distant lesions that were pathologically examined due to a suspicious aspect on SSTR PET/CT, a positive predictive value (PPV) of 100% was observed.

CONCLUSION: Our findings confirm the higher SSTR ligand uptake in TC compared to AC and vice versa for [¹⁸F]FDG uptake. More importantly, we found a good diagnostic performance of SSTR PET/CT for the detection of hilar and mediastinal lymph node metastases of TC. Finally, a PPV of 100% for SSTR PET/CT was found in a small sub-cohort of patients with pathologically investigated distant metastatic lesions. Taken together, SSTR PET/CT has a very high diagnostic value in the TNM assessment of pulmonary carcinoids, particularly in TC, which underscores its position in European guidelines.

PMID:35524900 | DOI:10.1186/s13550-022-00900-3

J Patient Rep Outcomes. 2022 May 7;6(1):44. doi: 10.1186/s41687-022-00452-z.

ABSTRACT

BACKGROUND: Chronic pain management multi/interdisciplinary programs attempt to address all elements of the biopsychosocial model. The primary objective of this retrospective study (based on practice-based audit) was to determine the effectiveness of a patient-centered, comprehensive and intense interdisciplinary pain management program in a publicly funded community-based pain clinic in the Greater Toronto Area.

METHOD: This retrospective longitudinal study was conducted on 218 carefully selected sequential chronic pain patients, with 158 completing a 3-4-month interdisciplinary program between January 2016 and December 2018. Data collected upon exit, at 6 months and 12 months post-discharge included demographic information, pain characteristics, emotional/functional status obtained by validated instruments and global impression of change (GIC). Additionally, social health outcomes (return to work or school) were retrieved through retrospective chart review. Means of pre-and post-program variables were compared to assess changes of each patient’s “journey”.

RESULTS: Physical and mental/ emotional health outcomes at exit, 6 months and 12 months post-discharge, showed initial and sustained, statistically and clinically significant improvement from pre-treatment levels, with GIC (much/very much improved) reported as 77%, 58% and 76%, respectively. Additionally, a substantial positive change in social health outcomes was noted particularly in patients on disability (29%), part time workers gaining full time employment (55%), and students (71%) who improved their level of schooling.

CONCLUSION: The study showed that careful patient selection in a community-based publicly funded interdisciplinary pain management program can produce significant improvement in pain, physical, mental/emotional health and social function, with sustained long-term outcomes.

PMID:35524863 | DOI:10.1186/s41687-022-00452-z

Environ Sci Pollut Res Int. 2022 May 7. doi: 10.1007/s11356-022-20435-3. Online ahead of print.

ABSTRACT

The digital economy, which gradually emerged with a new generation of information technologies, has become an unavoidable reality for manufacturing firms in conducting green innovation activities. In this context, using matched panel data at the province and manufacturing firm levels in China during the period 2011-2019 as the sample, this article examines the nonlinear impact of the digital economy on firm green innovation, and further identifies the moderation mechanism of government quality and the heterogeneity of its effects. The two-way fixed-effects model reveals that there is not a simple linear association between the digital economy and firm green innovation as traditionally perceived, but rather an inverted U-shaped relationship that first promotes and then inhibits, which remains robust after applying endogenous and robustness tests. And most provinces have not yet crossed the inflection point; thus, the digital economy overall positively impacts green innovation. Further analysis shows that government quality positively moderates the relationship between the digital economy and firm green innovation, statistically reflecting that the turning point shifts upwards to the right under a higher-quality government. It is worth noting that, when heterogeneity in firm ownership, scale, and region is considered, the inverted U-shaped curve still exists, but the level of the digital economy at the inflection point differs, and the digital economy plays a greater role in promoting green innovation for state-owned, large-scale, or midwestern firms. This research has significant policy implications as it establishes an inverse U-shaped relationship between the digital economy and firm green innovation and indicates that while a firm’s green patent output increases with the development of digitalization, it begins to decrease after a limit.

PMID:35524847 | DOI:10.1007/s11356-022-20435-3

Adv Ther. 2022 May 7. doi: 10.1007/s12325-022-02166-6. Online ahead of print.

ABSTRACT

INTRODUCTION: The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy.

METHODS: A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6.

RESULTS: The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (p < 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7 (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup (p = 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users (p < 0.001).

CONCLUSION: PF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively.

CLINICAL STUDY NUMBER: European Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204.

PMID:35524840 | DOI:10.1007/s12325-022-02166-6

Curr Microbiol. 2022 May 7;79(6):186. doi: 10.1007/s00284-022-02882-w.

ABSTRACT

Although persistent sustained viral response rates are increased in hepatitis C infection following administration of direct-acting antiviral (DAA) agents, the pre-use predictive parameters of these antivirals and the clinical progression in patients post-treatment remain unknown. To obtain data pertaining to the predictive parameters prior to the use of ombitavir/paritaprevir/ritonavir + dasabuvir and the clinical progression in patients following antiviral treatment. The expression profiles of miR-223-3p, miR-17-5p, miR-24-3p, and TLR2 – 196 to – 174 del/ins polymorphisms from the blood/serum of 34 hepatitis C virus (HCV)-infected patients pre- and post-ombitavir/paritaprevir/ritonavir + dasabuvir treatment were determined by RT-qPCR. The expression levels of miR-17-5p (P < 0.001) and miR-24-3p (P = 0.011) were significantly downregulated post-treatment as compared with those pre-treatment; however, there was no significant difference between these two groups in terms of miR-223-3p expression. In addition, there was no significant difference in TLR2 genotype or allele distribution between pre-and post-treatment (P > 0.05); nevertheless, the TLR2 del allele was decreased post-treatment (16.2%) as compared with that pre-treatment (19.1%), although the difference was not statistically significant. Moreover, a significant difference was found between the mRNA levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and HCV RNA pre-and post-treatment (P < 0.05). Further, miR-17-5p expression correlated with both ALT and AST mRNA levels post-treatment (P.

PMID:35524830 | DOI:10.1007/s00284-022-02882-w

Int J Legal Med. 2022 May 7. doi: 10.1007/s00414-022-02834-w. Online ahead of print.

ABSTRACT

It is difficult to determine the cause of death in electric shock injuries when no trace can be determined on the skin, and this is accepted as a reason for negative autopsy. We aimed to determine useful parameters in the definition of the cause of deaths associated with electric shock and particularly those formed with water conduction. This study used a total of 42 rats, applied with fatal electric shock formed of isolated electric shock at 220 V and with water conduction. The serum NT-ProBNP and H-FABP levels were examined together with histopathological changes in the brain, cerebellum, brainstem, heart, liver and skin and the Bax, caspase-3 and HSP-60 antibody status in these tissues. A statistically significant difference was determined between the groups in respect of the serum H-FABP values and the immunohistochemical staining of the samples taken from the organs. In conclusion, this study is the first in literature with an experimental model of electric shock with water conduction. Using immunohistochemical and biochemical markers in deaths associated with isolated electric shock and electric shock with water conduction, the results of this study can contribute to the clarification of one of the reasons for negative autopsy in forensic medicine.

PMID:35524806 | DOI:10.1007/s00414-022-02834-w

Int Orthop. 2022 May 7. doi: 10.1007/s00264-022-05421-1. Online ahead of print.

ABSTRACT

PURPOSE: Diagnosing periprosthetic joint infections (PJI) are challenging and may be hampered by the presence of other causes of local inflammation. Conventional synovial and serum markers are not reliable under these circumstances. Synovial calprotectin has been recently shown as a promising biomarker for PJI in total hip (THA) and total knee arthroplasty (TKA). The aim of this study is to investigate if calprotectin is reliable for PJI diagnosis in cases with accompanying inflammation due to recent surgery, dislocation or implant breakage in primary and revision TKA and THA.

METHODS: Thirty-three patients were included in this prospective study between July 2019 and October 2021 (17 patients undergoing surgery < 9 months, 11 dislocations, five implant breakage, respectively). Synovial white blood cell count (WBC), percentage of polymorphonuclear neutrophils (PMC), serum C-reactive protein (CRP) and synovial calprotectin, using a lateral-flow-assay, were analysed. These parameters were tested against a modified European-Bone-and-Joint-Infection-Society (EBJIS) definition with adjusted thresholds to account for the local inflammation. Statistic quality criteria were calculated and compared using a binary classification test.

RESULTS: Seventeen patients were classified as confirmed infections according to the modified EBJIS definition (13 THA and 4 TKA). The calprotectin assay yielded a sensitivity of 0.88 (0.64, 0.99), a specificity of 0.81 (0.54, 0.96), a positive predictive value (PPV) of 0.83 (0.59, 0.96) and a negative predictive value (NPV) of 0.87 (0.60, 0.98).

CONCLUSIONS: Even in the presence of local inflammation due to other, non-infectious causes, calprotectin is a reliable diagnostic parameter for the detection of a PJI in primary and revision THA and TKA.

PMID:35524793 | DOI:10.1007/s00264-022-05421-1

Pediatr Surg Int. 2022 May 7. doi: 10.1007/s00383-022-05133-y. Online ahead of print.

ABSTRACT

BACKGROUND: The fragility index has been gaining ground in the evaluation of comparative clinical studies. Many scientists evaluated trials in their fields and deemed them to be fragile, although there is no consensus on the definition of fragility. We aimed to calculate the fragility index and its permutations for paediatric surgical trials.

METHODS: We searched pubmed for prospectively conducted paediatric surgical trials with intervention and control group without limitations and calculated their (reverse) fragility indices and respective quotients along with posthoc-power. Relationships between variables were evaluated using Spearman’s ρ. We also calculated S values by negative log transformation base-2 of P values.

RESULTS: Of 516 retrieved records, we included 87. The median fragility index was 1.5 (interquartile range: 0-4) and the median reverse fragility index was 3 (interquartile range: 2-4), although they were statistically not different (Mood’s test: χ² = 0.557, df = 1, P = 0.4556). P values and fragility indices were strongly inversely correlated (ρ = – 0.71, 95% confidence interval: – 0.53 to – 0.85, P < 0.0001), while reverse fragility indices were moderately correlated to P values (ρ = 0.5, 95% confidence interval: 0.37-0.62, P < 0.0001). A fragility index of 1 resulted from P values between 0.039 and 0.003, which resulted in S values between 4 and 8.

CONCLUSIONS: Fragility indices, reverse fragility indices, and their respective fragility quotients of paediatric surgical trials are low. The fragility index can be viewed as no more than a transformed P value with even more substantial limitations. Its inherent penalisation of small studies irrespective of their clinical relevance is particularly harmful for paediatric surgery. Consequently, the fragility index should be avoided.

PMID:35524787 | DOI:10.1007/s00383-022-05133-y

J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2022 May 7. doi: 10.1007/s00359-022-01553-2. Online ahead of print.

ABSTRACT

Peer review, a core element of the editorial processing of manuscripts submitted for publication in scientific journals, is widely criticized as being flawed. One major criticism is that many journals allow or request authors to suggest reviewers, and that these ‘preferred reviewers’ assess papers more favorably than do reviewers not suggested by the authors. To test this hypothesis, a retrospective analysis was conducted of 162 manuscripts submitted to the Journal of Comparative Physiology A between 2015 and 2021. Out of these manuscripts, 83 were finally rejected and 79 were finally accepted for publication. In neither group could a statistically significant difference be detected in the rating of manuscripts between reviewers suggested by the authors and reviewers not suggested by the authors. Similarly, pairwise comparison of the same manuscripts assessed by one reviewer suggested by the authors and one reviewer not suggested by the authors did not reveal any significant difference in the median recommendation scores between these two reviewer types. Thus, author-suggested reviewers are not necessarily, as commonly assumed, less neutral than reviewers not suggested by the authors, especially if their qualification and impartiality is vetted by the editor before they are selected for peer review.

PMID:35524786 | DOI:10.1007/s00359-022-01553-2

J Cancer Res Clin Oncol. 2022 May 7. doi: 10.1007/s00432-022-04031-z. Online ahead of print.

ABSTRACT

OBJECTIVES: This study investigates whether lead-time bias contributes to the excellent survival of AIS and MIA.

METHODS: We enrolled patients with resected adenocarcinoma from 2008 to 2012. Age, sex, smoke history, surgical approach, radiological features, invasive stage and postoperative follow-up data were documented. 1:1 PSM was performed to balance the influence of sex and smoking status on survival. After matching, the average age of the two groups was compared to calculate the lead time of diagnosis. The gain in life years for adenocarcinoma diagnosed at pre-/minimally invasive stage was estimated by subtracting the “lead time” and “median survival year of IAC” from “the life expectancy of AIS/MIA patients” referring to the Centre for Health and Information.

RESULTS: There were 124 AIS/MIA patients and 1148 IAC patients. The frequency of female and never-smoking patients in AIS/MIA group was much higher than that in IAC group. PSM analysis identified 124 patient pairs. No cancer-related death and recurrence were observed among AIS/MIA patients 5 years after surgery. For IAC patients, the 5-year disease-specific survival rate was 73.5% and the median survival is 13.5 years. The average age of AIS/MIA group and IAC group are 53.6 years and 58.2 years, respectively. The lead time between diagnosis of AIS/MIA and IAC is 4.6 years. Referring to the Centre for Health and Information, the life expectancy of patients with AIS/MIA diagnosed at 53.6 years old is 28.9 years. With adjustment for the lead time, the gain in life years for adenocarcinoma diagnosed at pre-/minimally invasive stage is 10.8 years.

CONCLUSIONS: With adjustment for the lead time between diagnosis of AIS/MIA and IAC, resecting lung adenocarcinoma at pre-/minimally invasive stage can improve life expectancy. The excellent survival of AIS/MIA is not lead-time bias.

PMID:35524781 | DOI:10.1007/s00432-022-04031-z