Nevin Manimala

J Obstet Gynaecol Can. 2021 Aug 30:S1701-2163(21)00611-3. doi: 10.1016/j.jogc.2021.07.021. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare surgical and oncological outcomes in the treatment of endometrial cancer between laparotomy and minimally invasive surgery. The secondary objective was to determine which MIS approach was the most beneficial.

METHODS: This was a single-centre retrospective review of all endometrial cancer surgeries performed between November 1, 2012 and October 31, 2017 in a gynaecologic oncology unit of a university hospital. Descriptive statistics were used to compare histopathologic results and oncological outcomes, and Kaplan-Meier estimates were used to compare survival.

RESULTS: A total of 735 cases were reviewed. The majority of patients (77%) underwent either laparotomy (35%) or robotic-assisted hysterectomy (42%); the remaining patients underwent total laparoscopic hysterectomy (12%) or a laparoscopic-assisted vaginal hysterectomy (8.7%). There was a statistically significant overall survival benefit (P = 0.02), a shorter hospital stay (P < 0.0001), and fewer early surgical complications (<30 d; P = 0.0002), as well as a survival benefit in elderly patients (>70 y) in the robotic-assisted hysterectomy group (P = 0.043) than the laparotomy group. Operating time was shorter in the laparotomy group (P < 0.0001). Recurrence rates in stage 1 low-risk disease were similar between groups.

CONCLUSION: Minimally invasive surgical approaches, particularly robotic surgery, do not compromise oncologic outcomes, especially for early-stage low-risk disease. In addition, these approaches are associated with fewer early surgical complications and shorter hospital stay, with significantly more same-day discharges. Overall survival and survival in a subgroup of elderly patients were significantly better in the robotic-assisted hysterectomy group.

PMID:34474173 | DOI:10.1016/j.jogc.2021.07.021

Transplant Cell Ther. 2021 Aug 30:S2666-6367(21)01169-6. doi: 10.1016/j.jtct.2021.08.020. Online ahead of print.

ABSTRACT

INTRODUCTION: Each year more than 8,000 allogeneic stem cell transplantations (allo-SCT) are performed in the United States and approximately 30% of these patients are ≥60 years old. Allo-SCT cases have increased risk to develop human papillomavirus (HPV)-related precancer or second malignancy. It is important to evaluate HPV-related precancer or second malignancy among allo-SCT cases to develop or enhance screening and preventive practice guidelines to improve patients’ survival and quality of life.

OBJECTIVE: We estimated the cumulative incidence of HPV-related precancer or second malignancy in both male and female Medicare beneficiaries who received allo-SCT and compared it with non-SCT controls and non-cancer controls.

MATERIALS AND METHODS: This is a retrospective matched case control study. Hematologic cancer patients aged ≥18 years who received allo-SCT between 2002 and 2011 were matched 1:5 to non-SCT controls and to non-cancer controls by age, sex, race/ethnicity, and follow-up time. Proportions of HPV-related precancer or second malignancy were estimated and compared between cases and controls using Chi-square test and logistic regression. Kaplan-Meier cumulative incidences were estimated and compared using log rank tests.

RESULTS: We identified 700 allo-SCT cases (median age of 64 years and median follow-up time post-transplant of 4.3 years) matched with 3159 non-SCT controls and 3302 non-cancer controls. About 3.7% of allo-SCT cases developed HPV-related precancer or second malignancy post-transplant, compared with 1.9% in the non-SCT controls and 1.1% in the non-cancer controls. The odds ratio of developing HPV-related precancer or second malignancy of allo-SCT cases compared with non-SCT controls and non-cancer controls was 2.0 (95% confidence interval [CI]: 1.25-3.18) and 3.5 (95% CI: 2.1-5.8), respectively. Both allo-SCT cases and non-SCT controls had significantly higher proportions and odds in developing HPV-related precancer or second malignancy than non-cancer controls. The 5-year cumulative incidence in allo-SCT cases was 5% compared with 2.1% in non-SCT controls and 1.2% in non-cancer controls. The cumulative incidence of HPV-related precancer or second malignancy in the allo-SCT was statistically significantly higher than either of the two matched control groups, and non-SCT controls had a higher cumulative incidence of HPV-related precancer or second malignancy than that in non-cancer controls.

DISCUSSION: Allo-SCT cases were at increased risk of developing HPV-related precancer or second malignancy compared with non-SCT controls and non-cancer controls. Routine screening of HPV-related precancer or second malignancy in allo-SCT cases is needed to prevent HPV-related precancer or second malignancy.

PMID:34474166 | DOI:10.1016/j.jtct.2021.08.020

Transplant Cell Ther. 2021 Aug 30:S2666-6367(21)01170-2. doi: 10.1016/j.jtct.2021.08.021. Online ahead of print.

ABSTRACT

BACKGROUND: Acute graft-versus-host disease (GVHD) is a major cause of mortality in patients receiving hematopoietic cell transplantation (HCT) for hematologic malignancies. The skin is the most commonly involved organ in GVHD. Elafin, a protease inhibitor overexpressed in inflamed epidermis, was previously identified as a diagnostic biomarker of skin GVHD. However, this finding was restricted to a subset of patients with isolated skin GVHD. The main driver of nonrelapse mortality (NRM) in HCT patients is GI GVHD. Two biomarkers, Regenerating islet-derived 3a (REG3a) and Suppressor of tumorigenesis 2 (ST2), have been validated as biomarkers of GI GVHD that predict long-term outcomes in patients treated for GVHD. We undertook this study to determine the utility of elafin as a prognostic biomarker in the general population of acute GVHD patients in whom GVHD may develop in multiple organs.

OBJECTIVE: To analyze serum elafin concentrations as a predictive biomarker of acute GVHD outcomes and to compare it to ST2 and REG3a in a large group of patients treated at multiple centers.

STUDY DESIGN: 526 patients who received corticosteroid treatment for skin GVHD and who had not been previously studied were analyzed from the Mount Sinai Acute GVHD International Consortium (MAGIC). Serum concentrations of elafin, ST2 and REG3a were measured for all patients using ELISA. Patients were divided randomly into equal training and validation sets and a competing risk regression model was developed to model 6-month NRM using elafin concentration in the training set. Additional models were developed using concentrations of ST2 and REG3a, or the combination of all three biomarkers as predictors. ROC curves were constructed using the validation set to evaluate the predictive accuracy of each model and to stratify patients into high- and low-risk biomarker groups. The cumulative incidence of 6-month NRM, overall survival, and four-week treatment response were compared between risk groups.

RESULTS: Patients in the low-risk elafin group unexpectedly demonstrated a higher incidence of 6-month NRM, although this difference was not statistically significant (17% vs. 11%, P=0.19). Overall survival at 6 months (68% vs. 68%, P>0.99) and four-week response (78% vs. 78%, P=0.98) were similar in the low- and high-risk elafin groups. The area under the receiver operating curve (AUROC) for elafin was 0.55 whereas it was 0.75 for the combination of ST2 and REG3a. The addition of elafin to the other two biomarkers did not improve the AUROC.

CONCLUSION: Serum elafin concentrations measured at the initiation of systemic treatment for acute GVHD do not predict 6-month NRM, overall survival, or treatment response in a multicenter population of patients treated systemically for acute GVHD. As seen in previous studies, serum concentrations of the GI GVHD biomarkers ST2 and REG3a were significant predictors of NRM and the addition of elafin levels did not improve their accuracy. These results underscore the importance of GI disease in driving NRM in patients who develop acute GVHD.

PMID:34474163 | DOI:10.1016/j.jtct.2021.08.021

J Shoulder Elbow Surg. 2021 Aug 30:S1058-2746(21)00643-1. doi: 10.1016/j.jse.2021.07.027. Online ahead of print.

ABSTRACT

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) has proven to be a highly effective treatment for rotator cuff deficient conditions and other end-stage shoulder pathologies. With value-based care emerging, identifying predictive factors of outcomes are of great interest. Although preoperative opioid use has been shown to predict inferior outcomes after anatomic total shoulder arthroplasty and rotator cuff repair, there is a paucity of data regarding its effect on outcomes after RTSA. We analyzed a series of RTSAs to determine the influence of preoperative opioid use on clinical and radiographic outcomes at a minimum of 2 years follow-up.

METHODS: A retrospective review of primary RTSA patient data revealed 264 patients with at least 2 years of clinical and radiographic follow-up. Patients were classified as preoperative opioid users (71 patients) if they had taken narcotic pain medication for a minimum of 3 months prior to surgery or opioid-naive (193 patients) at the time of surgery. Assessments included preoperative and postoperative visual analog pain scores (VAS), American Shoulder and Elbow Surgeons (ASES) scores, strength, range of motion (ROM), complications, and revisions. Radiographs were analyzed for signs of loosening or mechanical failure. Mann-Whitney U and Fisher exact tests were used for comparisons between groups. Statistical significance was set at p < 0.05.

RESULTS: The mean patient age was 69.9 years, and the mean follow-up time was 2.8 years. Opioid users were significantly younger (66.1 vs. 70.7 years, p < 0.001) at time of surgery and had significantly higher preoperative rates of mood disorders, chronic pain disorders, and disability status (all p < 0.05). Postoperatively, opioid users had inferior VAS (2.59 vs 1.25, p < 0.001), ASES scores (63.2 vs 75.2, p < 0.001), active forward elevation (p < 0.001), and internal and external rotational shoulder strength (all p < 0.05) than opioid-naïve patients. Periprosthetic radiolucency (8.45% vs 2.07%, p = 0.026) and subsequent revision arthroplasty (14.1% vs 4.66%, p = 0.014) occurred more frequently in opioid users than opioid-naïve patients. Both groups improved from baseline preoperatively to most recent follow-up in terms of functional outcomes and pain.

CONCLUSION: Preoperative opioid use portended markedly inferior clinical outcomes in patients undergoing RTSA. Additionally, opioid users had significantly increased rates of periprosthetic radiolucency and revisions. Preoperative opioid use appears to be a significant marker for adverse outcomes after RTSA.

PMID:34474138 | DOI:10.1016/j.jse.2021.07.027

Ann Vasc Surg. 2021 Aug 30:S0890-5096(21)00560-4. doi: 10.1016/j.avsg.2021.06.018. Online ahead of print.

ABSTRACT

BACKGROUND: The UK has one of the highest rates of recreational drug use and consequent deaths in Europe. Scotland is the “Drugs death capital of Europe.” Intravenous drug use can result in limb- and life-threatening pathology. This study aimed to characterise limb-related admissions associated with intravenous drug use, outcomes and healthcare expenditure.

METHODS: Retrospective data collection between December 2011-August 2018. Patients were identified through discharge codes. Admission details were extracted from electronic records and a database compiled. Statistical analyses were performed using Statistical Package for the Social Science, p<0.05 denoted significance.

RESULTS: There were 558 admissions for 330 patients (1-9 admissions/patient), mean age 37 years (+/-7.6 SD) and 196 (59.2%; 319 admissions, 57.2%) were male. 348 (62.4%) admissions were to surgical specialties, predominantly Vascular Surgery (247). Including onward referrals, Vascular ultimately managed 54.8% of admissions. Patients presented with multiple pathologies: 249 groin abscesses; 38 other abscesses; 74 pseudoaneurysms; 102 necrotising soft tissue infections (NSTI); 85 cellulitis; 138 DVTs; 28 infected DVTs and 70 other diagnoses. 277 admissions (220 patients) required operations, with 361 procedures performed (1-7 operations/admission). There were 24 major limb amputations and 74 arterial ligations. 11 amputations were due to NSTI and 13 followed ligation (17.6% of ligations). During follow-up 50 (15.2%) patients died, of which six (12%) had amputations (OR 3.2, 95% CI 1.04-9.61, p=0.043). Cumulative cost of acute care was £4,783,241.

CONCLUSION: Limb-related sequalae of intravenous drug use represents a substantial surgical workload, especially for Vascular. These are complex, high-risk patients with poor outcomes and high healthcare costs.

PMID:34474130 | DOI:10.1016/j.avsg.2021.06.018

Pharmacol Res. 2021 Aug 30:105863. doi: 10.1016/j.phrs.2021.105863. Online ahead of print.

NO ABSTRACT

PMID:34474101 | DOI:10.1016/j.phrs.2021.105863

Int J Biostat. 2021 Sep 2. doi: 10.1515/ijb-2020-0046. Online ahead of print.

ABSTRACT

Interrupted time series (ITS) design is commonly used to evaluate the impact of interventions in healthcare settings. Segmented regression (SR) is the most commonly used statistical method and has been shown to be useful in practical applications involving ITS designs. Nevertheless, SR is prone to aggregation bias, which leads to imprecision and loss of power to detect clinically meaningful differences. The objective of this article is to present a weighted SR method, where variability across patients within the healthcare facility and across time points is incorporated through weights. We present the methodological framework, provide optimal weights associated with data at each time point and discuss relevant statistical inference. We conduct extensive simulations to evaluate performance of our method and provide comparative analysis with the traditional SR using established performance criteria such as bias, mean square error and statistical power. Illustrations using real data is also provided. In most simulation scenarios considered, the weighted SR method produced estimators that are uniformly more precise and relatively less biased compared to the traditional SR. The weighted approach also associated with higher statistical power in the scenarios considered. The performance difference is much larger for data with high variability across patients within healthcare facilities. The weighted method proposed here allows us to account for the heterogeneity in the patient population, leading to increased accuracy and power across all scenarios. We recommend researchers to carefully design their studies and determine their sample size by incorporating heterogeneity in the patient population.

PMID:34473922 | DOI:10.1515/ijb-2020-0046

Int J Clin Pract. 2021 Sep 2:e14766. doi: 10.1111/ijcp.14766. Online ahead of print.

ABSTRACT

BACKGROUND: Iodinated contrast media (ICM) – frequently used compound in radiology. Non-immediate hypersensitivity reactions (HSR) appear when a patient leaves the department and usually are undocumented. True hypersensitivity in this group is rarely proved.

METHODS: Single-center 2014-2018 data was retrospectively analysed. HSR to ICM were classified and investigated according to the time of occurrence (immediate <1h, non-immediate >1h). ENDA questionnaire and skin tests (prick or intradermal test) were performed according to ENDA/EAACI recommendations.

RESULTS: 69 patients with a clinical history of HSR to ICM were identified, 72.46% were females (n=50). Average age was 56 (SD ± 13.16) years. Non-immediate HSR occurred in 28.99% (n=20) patients. The suspected culprit drugs were: iodixanol 20% (n=4), iopromide 5% (n=1), diatrizoate 10% (n=2), iohexol 10% (n=2). Among non-immediate HSR 96.00% (n=19) of patients had skin rashes. A statistically significant correlation was found between the clinical symptoms and the type of reaction (p-value < 0,05): isolated skin manifestations mostly occurred in non-immediate HSR 75.00% (n=15). Only 13.04% (n=9) of all the patients were proved to be allergic to a certain ICM after the proposed diagnostic workup.

CONCLUSIONS: One third of the hypersensitivity reactions investigated were classified as non-immediate type. Most of them manifested with isolated skin symptoms. The most frequent culprit drug encountered was iodixanol. The overall non-immediate hypersensitivity confirmation rate after diagnostic evaluation was only 15%.

PMID:34473887 | DOI:10.1111/ijcp.14766

Diabet Med. 2021 Sep 2:e14685. doi: 10.1111/dme.14685. Online ahead of print.

ABSTRACT

AIMS: This study aimed to evaluate the ability of HbA1c combined with glycated albumin (GA) or 1,5-anhydroglucitol (1,5-AG) to detect diabetes in residents of Jiangsu, China.

METHODS: The oral glucose tolerance test (OGTT) was performed on 2,184 people in Jiangsu. HbA1c, GA, 1,5-AG, and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA1c, GA, and 1,5-AG according to the Youden index.

RESULTS: (1) The optimal thresholds of HbA1c, GA, and 1,5-AG for the screening of diabetes were ≥ 45 mmol/mol (6.3%), ≥ 13.0%, and ≤ 23.0 μg/ml, respectively. (2) The sensitivities of HbA1c combined with GA and 1,5-AG were both 85%, higher than that of HbA1c (70%, P < 0.001).

CONCLUSIONS: This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA1c combined with GA or 1,5-AG can improve the sensitivity of diabetes screening, reduce the miss rate, and save the use of OGTT. GA and 1,5-AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5-AG enhances the detection in those with hyperuricemia.

PMID:34473869 | DOI:10.1111/dme.14685

Psychophysiology. 2021 Sep 2:e13933. doi: 10.1111/psyp.13933. Online ahead of print.

ABSTRACT

Non-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. The objective of this analysis was to synthesize the current evidence concerning the effects of taVNS on vagally mediated heart rate variability (vmHRV), a candidate biomarker that has, so far, received most attention in the field. We performed a living Bayesian random effects meta-analysis. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 16 single-blind studies comparing taVNS versus sham in healthy participants. The meta-analysis provides strong evidence for the null hypothesis (g = 0.014, CI_shortest = [-0.103, 0.132], BF₀₁ = 24.678), indicating that acute taVNS does not alter vmHRV compared to sham. To conclude, there is no support for the hypothesis that vmHRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.

PMID:34473846 | DOI:10.1111/psyp.13933