Comparative study on short-term efficacy of single incision plus one (SI+1) port and multiportal 3D laparoscopic minimally invasive esophagectomy

BackgroundTo evaluate the safety and efficacy of single incision plus one (SI+1) port three-dimensional (3D) laparoscopic minimally invasive esophagectomy (MIE).MethodsClinical data of patients who underwent 3D thoracic laparoscopic MIE in our department from September 2020 to March 2021 were analyzed retrospectively. According to the different methods of laparoscopic surgery, the patients were divided into 2 groups: SI+1 port 3D laparoscopy group and multiportal 3D laparoscopy group. The operation time of the 3D laparoscopy component, amount of intraoperative blood loss, number of celiac lymph node dissections, postoperative abdominal drainage days, postoperative total abdominal drainage, postoperative complications, and length of hospital stay were analyzed.ResultsThere was no significant difference between the 2 methods in laparoscopic operation time (30.11±5.86 vs. 28.45±4.72 min, P=0.49), intraoperative blood loss (34.44±9.82 vs. 35.91±6.25 mL, P=0.69), number of celiac lymph node dissections (8.44±3.13 vs. 7.09±2.12, P=0.27), postoperative abdominal drainage days (3.11±0.33 vs. 3.00±0.00 days, P=0.28), postoperative total abdominal drainage (95.00±23.33 vs. 92.27±11.26 mL, P=0.74), postoperative complications (22.2% vs. 27.3%, P=0.33), and hospital stay (9.67±0.71 vs. 10.18±0.87 days, P=0.17). None of the patients enrolled in the study had recurrence or death to date.ConclusionsThe application of SI+1 port 3D laparoscopy in minimally invasive resection of esophageal carcinoma is safe and feasible.     

Laparoscopic-assisted versus open proximal gastrectomy with double-tract reconstruction for Siewert type II–III adenocarcinomas of esophago-gastric junction: a retrospective observational study of short-term outcomes

BackgroundCurrently, the surgical approach to adenocarcinomas of esophago-gastric junction (AEG) remains controversial. Function-preserving gastric surgeries are becoming more popular, with proximal gastrectomy with double-tract anastomosis being one of the most important for AEG. Meanwhile, with the increasing use of laparoscopic techniques in the treatment of gastric cancer, the safety and effectiveness of laparoscopic-assisted proximal gastrectomy with double-tract anastomosis for Siewert type II–III AEG need to be further clarified.MethodsData of patients with Siewert type II/III AEG was collected at our center from October 2010 to December 2019 were retrospectively analyzed. 61 patients underwent open proximal gastrectomy with double-tract anastomosis (OPG-DT group) and 52 underwent laparoscopic-assisted proximal gastrectomy with double-tract anastomosis (LAPG-DT group). The clinical features, surgery, and short-term outcomes of patients in these 2 groups were collected to assess the safety and feasibility of LAPG-DT.ResultsA total of 113 patients were analyzed, there were 98 males and 15 females. No death during the operation. The differences in the number of lymph nodes, time to first flatus time to first eating, postoperative hospital stay, Additional analgesics were not statistically significant between two groups. Although the operative duration of LAPG-DT group was significantly longer than that of the OPG-DT group [(217±61) vs. (161±14) min, P=0.000), while less blood loss and less stress in LAPG-DT group. Early and late postoperative complications were similar between two groups.ConclusionsAlthough laparoscopic-assisted proximal gastrectomy with double-tract anastomosis requires long operative time, it is associated with less bleeding and milder stress. Therefore, it is a safe and feasible surgical method.     

Effect of Poloxamer-Based Thermo-Sensitive Sol-Gel Agent on Upper Limb Dysfunction after Axillary Lymph Node Dissection: A Double-Blind Randomized Clinical Trial

PurposeRestricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer. This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND.MethodsWe designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period).ResultsA total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (−30.04 ± 27.76 vs. −42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (−3.92 ± 9.80 vs. −10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group.ConclusionWe suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02967146","term_id":"NCT02967146"}}NCT02967146     

Complement C3a activates osteoclasts by regulating the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma

Objective:Myeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease. However, the mechanism of C3a/C4a in osteoclasts MM patients remains unclear.Methods:The formation and function of osteoclasts were analyzed after adding C3a/C4a in vitro. RNA-seq analysis was used to screen the potential pathways affecting osteoclasts, and the results were verified by Western blot, qRT-PCR, and pathway inhibitors.Results:The osteoclast area per view induced by 1 μg/mL (mean ± SD: 50.828 ± 12.984%) and 10 μg/mL (53.663 ± 12.685%) of C3a was significantly increased compared to the control group (0 μg/mL) (34.635 ± 8.916%) (P < 0.001 and P < 0.001, respectively). The relative mRNA expressions of genes, OSCAR/TRAP/RANKL/cathepsin K, induced by 1 μg/mL (median: 5.041, 3.726, 1.638, and 4.752, respectively) and 10 μg/mL (median: 5.140, 3.702, 2.250, and 5.172, respectively) of C3a was significantly increased compared to the control group (median: 3.137, 2.004, 0.573, and 2.257, respectively) (1 μg/mL P = 0.001, P = 0.003, P < 0.001, and P = 0.008, respectively; 10 μg/mL: P < 0.001, P = 0.019, P < 0.001, and P = 0.002, respectively). The absorption areas of the osteoclast resorption pits per view induced by 1 μg/mL (mean ± SD: 51.464 ± 11.983%) and 10 μg/mL (50.219 ± 12.067%) of C3a was also significantly increased (33.845 ± 8.331%) (P < 0.001 and P < 0.001, respectively) compared to the control. There was no difference between the C4a and control groups. RNA-seq analysis showed that C3a promoted the proliferation of osteoclasts using the phosphoinositide 3-kinase (PI3K) signaling pathway. The relative expressions of PIK3CA/phosphoinositide dependent kinase-1 (PDK1)/serum and glucocorticoid inducible protein kinases (SGK3) genes and PI3K/PDK1/p-SGK3 protein in the C3a group were significantly higher than in the control group. The activation role of C3a in osteoclasts of MM patients was reduced by the SGK inhibitor (EMD638683).Conclusions:C3a activated osteoclasts by regulating the PI3K/PDK1/SGK3 pathways in MM patients, which was reduced using a SGK inhibitor. Overall, our results identified potential therapeutic targets and strategies for MBD patients.     

The expression and clinical value of tumor infiltrating dendritic cells in tumor tissues of patients with esophageal cancer

BackgroundAs dendritic cells (DCs) are the major antigen-presenting cells of the immune system, understanding their role in esophageal cancer is essential for the development of preventative and treatment strategies. This study investigated the expression level and clinical value of tumor infiltrating dendritic cells (TIDCs) in tumor tissues of patients with esophageal cancer.MethodsFrom January 2019 to January 2021, 184 patients with esophageal cancer treated were prospectively enrolled as the observation group and 184 patients with benign esophageal tumors were selected as the control group. Tumor tissue samples were obtained and the expression level and phenotypes of the TIDCs were analyzed. The correlation between TIDC expression and clinical characteristics of patients with esophageal cancer was investigated.ResultsThe density of the TIDCs in the observation group was lower than that in the control group (8.76±2.25 vs. 9.97±2.19; P=0.000). Furthermore, the percentage of major histocompatibility complex-II (MHC-II) positive DCs and the percentage of CD54 positive DCs were relatively lower in the observation group compared to the control group (6.60%±2.12% vs. 9.34%±2.41%; P=0.000 and 7.41%±2.36% vs. 9.98%±2.47%; P=0.000, respectively). Esophageal cancer patients with lymph node metastasis had lower TIDC density, lower percentage of MHC-II positive DCs, and lower percentage of CD54 positive DCs compared to patients without node metastasis (P<0.05). Patients with stage III esophageal cancer also showed significantly lower TIDC density, lower percentage of MHC-II positive DCs, and lower percentage of CD54 positive DCs compared to patients with stage I/II esophageal cancer (P<0.05). Esophageal cancer patients with tumor diameter ≥4 cm presented with decreased TIDC density, decreased percentage of MHC-II positive DCs, and decreased percentage of CD54 positive DCs compared to patients with tumor diameter <4 cm (P<0.05). In addition, the density of TIDCs, the percentage of MHC-II positive DCs, and the percentage of CD54 positive DCs were significantly negatively correlated with the percentage of CD4⁺ T-lymphocytes and positively correlated with the percentage of CD8⁺ T-lymphocytes (P<0.05).ConclusionsPatients with esophageal cancer had low expression and function of TIDCs, and this was related to the imbalance of T-lymphocyte subsets, lymph node metastasis, TNM stage, and lesion size.     

Comparison between Gasless and Gas-Inflated Robot-Assisted Nipple-Sparing Mastectomy

PurposeNipple-sparing mastectomy (NSM) includes various techniques, including conventional or endoscopic mastectomies. Since the introduction of robot-assisted NSM (RANSM) in 2015, 2 main methods have been used: gasless and gas-inflated techniques. The aim of this study was to compare clinicopathologic characteristics, surgical outcomes, and postoperative complications between patients treated with gasless RANSM and those treated with gas-inflated RANSM.MethodsWe conducted a retrospective study of women who underwent gasless or gas-inflated RANSM with immediate breast reconstruction between November 2016 and May 2019. The indications for RANSM were early breast cancer, interstitial mastopathy, or BRCA1/2 mutation carriers. Clinicopathologic characteristics, surgical outcomes, and postoperative complications were analyzed. The severity of complications was graded using the Clavien-Dindo system.ResultsA total of 58 RANSM procedures were performed in 46 women: 15 cases of gasless RANSM and 43 cases of gas-inflated RANSM. The proportion of node-negative disease was higher in the gas-inflated group (97.1%) than in the gasless group (69.2%, p = 0.016). Adjuvant radiotherapy was administered in 30.6% of the cases in the gasless group and only 5% of the cases in the gas-inflated group. Other clinicopathological factors were not significantly different between the groups. Regarding surgical outcomes, the initial incision was 1 cm longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.20 ± 1.05 cm; p = 0.002). The final incision was also longer in the gasless group (5.17 ± 0.88 cm) than that in the gas-inflated group (4.57 ± 1.07 cm; p = 0.040). Operation time, complication rate, and complication grade were not significantly different between the 2 groups.ConclusionIn this study, there were no significant differences in surgical outcomes or postoperative complications between gasless and gas-inflated RANSM, except for a longer incision with the gasless technique. Both techniques are reasonable options for RANSM followed by immediate reconstruction.     

Histological Findings of Mammary Gland Development and Risk of Breast Cancer in BRCA1 Mutant Mouse Models

PurposeThe breast cancer susceptibility gene, BRCA1, is involved in normal development and carcinogenesis of mammary glands. Here, we aimed to evaluate the relationship between histological findings of mammary gland development and breast cancer risk in BRCA1 mutant mice.MethodsFive BRCA1 mutant mice and five non-mutant FVB/NJ mice were used for each group of 1-month-old (pubertal), 3-month-old (fertile), and 8-month-old (menopausal) mice. In another experiment, 15 BRCA1 mutant mice were followed up to 8 months after birth and classified into tumor-bearing (11 mice) and tumor-free (4 mice) groups. Excised mammary gland tissues were stained with Carmine Alum, and the number of terminal end buds (or alveolar buds), branching density, and duct elongation were measured using image analysis programs. Differences between the two groups were assessed using paired t-test.ResultsOne-month-old BRCA1 mutant mice showed a higher number of terminal end buds (23.8 ± 1.0 vs. 15.6 ± 0.8, p = 0.0002), branching density (11.7 ± 0.4 vs. 9.6 ± 0.5%, p = 0.0082), and duct elongation (9.7 ± 0.7 vs. 7.3 ± 0.4 mm, p = 0.0186) than controls. However, there was no difference between the 3- and 8-month-old groups. In BRCA1 mutant mice, the tumor-bearing group showed a significantly higher number of alveolar buds (142.7 ± 5.5 vs. 105.5 ± 5.4, p = 0.0008) and branching density (30.0 ± 1.0 vs. 24.1 ± 1.1%, p = 0.008) than the tumor-free group; however, duct elongation was not different (23.9 ± 0.6 vs. 23.6 ± 0.6 mm, p = 0.8099) between the groups.ConclusionBRCA1 mutant mice exhibited early pubertal mammary gland development and delayed age-related mammary gland involution was associated with breast cancer. Our results may have clinical implications for predicting breast cancer risk and developing prevention strategies for BRCA1 mutation carriers.     

Ferritin as a diagnostic,differential diagnostic,and prognostic marker for immune-related adverse events

Objective:Distinguishing immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) from the AEs caused by chemotherapy, targeted therapy, or infection is highly difficult. This study offers new insights into evaluating the diagnosis, differential diagnostic, and prognostic value of ferritin for irAEs induced by ICIs.Methods:From December 1, 2018, to April 1, 2019, we examined 318 patients with malignant tumors who received serum ferritin monitoring. The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy, and 87 patients treated with chemotherapy. Of the 231 patients, 90 had irAEs (irAE group), 70 had non-irAEs (non-irAE group), 67 had no AEs (no irAE-non irAE group), and 4 had unclassified AEs. In the 87 patients, 60 had AEs (AE group), and 27 had no AEs (no AE group). Statistical analyses were conducted with nonparametric Mann-Whitney tests.Results:At the onset of AEs in the irAE group, ferritin (normal range, 35–150 µg/L) rose to a median of 927 µg/L (range, 117–17,825 µg/L) from 86 µg/L at baseline (range, 29–421 µg/L) (P < 0.001). Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group (median, 81 µg/L; range, 32–478 µg/L) (P < 0.001) and the AE group (median, 103 µg/L; range, 23–712 µg/L) (P < 0.001). After treatment in the irAE group, ferritin continuously decreased to a normal range in recovered patients, showed no significant changes in stable patients, and continued to rise in patients who died.Conclusions:Ferritin can be used as a diagnostic, differential diagnostic, and prognostic marker for irAEs in patients treated with ICIs.     

In vivo evaluation of percutaneous carbon dioxide treatment for improving intratumoral hypoxia using 18F-fluoromisonidazole PET-CT

Carbon dioxide (CO₂) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO₂ treatment in vivo was determined using ¹⁸F-fluoromisonidazole positron emission tomography-computed tomography (¹⁸F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO₂ treatment and ¹⁸F-FMISO PET-CT scans. Immediately after intravenous injection of ¹⁸F-FMISO, CO₂ and room air were administered transcutaneously in the CO₂-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of ¹⁸F-FMISO. ¹⁸F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUV_max), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO₂-treated group, 1.178±0.450 cm³; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUV_max, TLR, MTV (cm3) and TLG were significantly lower in the CO₂-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, ¹⁸F-FMISO PET revealed that percutaneous CO₂ treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO₂ treatment by imaging, and may contribute to its clinical application.     

Can Dynamic Imaging,Using 18F-FDG PET/CT and CT Perfusion Differentiate Between Benign and Malignant Pulmonary Nodules?

BackgroundThe aim of the study was to derive and compare metabolic parameters relating to benign and malignant pulmonary nodules using dynamic 2-deoxy-2-[fluorine-18]fluoro-D-glucose (¹⁸F-FDG) PET/CT, and nodule perfusion parameters derived through perfusion computed tomography (CT).Patients and methodsTwenty patients with 21 pulmonary nodules incidentally detected on CT underwent a dynamic ¹⁸F-FDG PET/CT and a perfusion CT. The maximum standardized uptake value (SUV_max) was measured on conventional ¹⁸F-FDG PET/CT images. The influx constant (K_i) was calculated from the dynamic ¹⁸F-FDG PET/CT data using Patlak model. Arterial flow (AF) using the maximum slope model and blood volume (BV) using the Patlak plot method for each nodule were calculated from the perfusion CT data. All nodules were characterized as malignant or benign based on histopathology or 2 year follow up CT. All parameters were statistically compared between the two groups using the nonparametric Mann-Whitney test.ResultsTwelve malignant and 9 benign lung nodules were analysed (median size 20.1 mm, 9–29 mm) in 21 patients (male/female = 11/9; mean age ± SD: 65.3 ± 7.4; age range: 50–76 years). The average SUV_max values ± SD of the benign and malignant nodules were 2.2 ± 1.7 vs. 7.0 ± 4.5, respectively (p = 0.0148). Average K_i values in benign and malignant nodules were 0.0057 ± 0.0071 and 0.0230 ± 0.0155 min^-1, respectively (p = 0.0311). Average BV for the benign and malignant nodules were 11.6857 ± 6.7347 and 28.3400 ± 15.9672 ml/100 ml, respectively (p = 0.0250). Average AF for the benign and malignant nodules were 74.4571 ± 89.0321 and 89.200 ± 49.8883 ml/100g/min, respectively (p = 0.1613).ConclusionsDynamic ¹⁸F-FDG PET/CT and perfusion CT derived blood volume had similar capability to differentiate benign from malignant lung nodules.Key words: pulmonary nodule, perfusion, CT, dynamic, PET/CT     

Longitudinal change in fine motor skills after brain radiotherapy and in vivo imaging biomarkers associated with decline

BackgroundWe explored fine motor skills (FMS) before and after brain radiotherapy (RT), analyzing associations between longitudinal FMS and imaging biomarkers of cortical and white matter (WM) integrity in motor regions of interest (ROIs).MethodsOn a prospective trial, 52 primary brain tumor patients receiving fractionated brain RT underwent volumetric brain MRI, diffusion tensor imaging, and FMS assessments (Delis-Kaplan Executive Function System Trail Making Test Motor Speed [DKEFS-MS], Grooved Pegboard Dominant Hands [PDH], and Grooved Pegboard Nondominant Hands [PNDH]) at baseline and 3-, 6-, and 12-month post-RT. Motor ROIs autosegmented included: sensorimotor cortices and superficial WM, corticospinal tracts, cerebellar cortices and WM, and basal ganglia. Volume (cc) was measured in all ROIs at each timepoint. Diffusion biomarkers (FA [fractional anisotropy] and MD [mean diffusivity]) were additionally measured in WM ROIs. Linear mixed-effects models assessed biomarkers as predictors of FMS scores. P values were corrected for multiple comparisons.ResultsHigher RT dose was associated with right paracentral cortical thinning (β = −2.42 Gy/(month × mm), P = .03) and higher right precentral WM MD (β = 0.69 Gy/(month × µm²/ms), P = .04). Higher left (β = 38.7 points/(month × µm²/ms), P = .004) and right (β = 42.4 points/(month × µm²/ms), P = .01) cerebellar WM MD, left precentral cortical atrophy (β = −8.67 points/(month × mm), P = .02), and reduced right cerebral peduncle FA (β = −0.50 points/month, P = .01) were associated with worse DKEFS-MS performance. Left precentral cortex thinning was associated with worse PDH scores (β = −17.3 points/(month × mm), P = .02). Left (β = −0.87 points/(month × cm³), P = .001) and right (β = −0.64 points/(month × cm³), P = .02) cerebellar cortex, left pons (β = −19.8 points/(month × cm³), P = .02), and right pallidum (β = −10.8 points/(month × cm³), P = .02) atrophy and reduced right internal capsule FA (β = −1.02 points/month, P = .03) were associated with worse PNDH performance.ConclusionsBiomarkers of microstructural injury in motor-associated brain regions were associated with worse FMS. Dose avoidance in these areas may preserve FMS.     

Serum MACC-1: a new biomarker for breast cancer

Metastasis-associated in colon cancer-1 (MACC-1) is a newly identified tumor marker, found to express in various normal and cancerous tissue. This study is conducted to evaluate the serum MACC-1 level as a diagnostic marker for breast cancer (BC). Sixty new BC patients were included in this study. Patients who received neoadjuvant chemotherapy or with metastatic disease were excluded. Eighty patients of benign disease were taken as control group. All the patients were females with the mean age of 46.7 ± 10.6 years in study group and 40.2 ± 8.4 years in control group (p = 0.0001). The mean serum MACC-1 level in BC patients was 3.46 ± 1.3 ng/ml which was significantly higher than control mean serum MACC-1 level (1.90 ± 0.2 ng/ml) (p < 0.0001). On ROC analysis, the AUC was 0.98 (p ≤ 0.0001; 95% CI = 0.97–1.0) i.e., a good predictor for breast cancer. At the cut-off value of 2.12 ng/ml, the sensitivity and the specificity of serum MACC-1 were 96.7% and 92.5%, respectively. This study showed that serum MACC-1 can be a potential biomarker for diagnosis and tumor progression in patients with breast cancer.     

Incidence and baseline characteristics of relapse or exacerbation in patients with pulmonary sarcoidosis in Japan

Background:To identify the incidence and baseline characteristics of relapse and exacerbation in patients with pulmonary sarcoidosis over a long-term period.Methods:We enrolled 103 patients. The incidence and characteristics of relapse or exacerbation were retrospectively recorded and statistically analysed.Results:Of 103 patients, 79% were women. Mean age at diagnosis was 50.1 ± 16.4 y. Mean observation period was 9.8 ± 8.6 y. Overall relapse or exacerbation was 22.3% (n = 23) and mean time from diagnosis (including diagnosis of ocular disease at another facility) to relapse or exacerbation was 8.7 ± 8.3 y. We analysed the data of 69 ­patients who were observed for > 5 y and identified relapse or exacerbation within 5 y in 9 patients. ­Comparison of characteristics at diagnosis between the relapse/exacerbation group and the improved/stable group showed that the relapse/exacerbation group had a significantly higher frequency of bilateral hilar lymphadenopathy, longer disease duration, ocular involvement, cardiac involvement, and oral glucocorticoid use at diagnosis (P = 0.014, 0.027, 0.019, 0.035, and 0.0043, respectively). The number of risk factors was positively and significantly associated with the cumulative rate of relapse/exacerbation (P = 0.048).Conclusion:Our long-term observational cohort study newly identified the incidence and baseline risk factors for relapse or exacerbation in patients with pulmonary sarcoidosis over a long-term period. Scoring the number of factors at baseline may facilitate the prediction of relapse or exacerbation.     

Putative role of prosthetic dental implants in the development of cardiac sarcoidosis: A case-control study

Background:Etiopathogenesis of cardiac sarcoidosis is poorly understood. The objective of this study is to examine a possible role of previous dental procedures on the development of cardiac sarcoidosis (CS).Methods:Clinical details of 73 patients with CS from the Granulomatous Myocarditis Registry were extracted. Data regarding clinical presentation, comorbidities, baseline electrocardiogram, echocardiogram, and ¹⁸fluorodeoxyglucose(FDG) PET-CT was extracted from the registry database. A comprehensive history of dental procedures for all patients was recorded. The two control groups comprised of 79 patients with idiopathic ventricular tachycardia and/or complete heart block (with similar clinical presentation) and 145 healthy age and sex matched patients, respectively.Results:Dental evaluation revealed that patients with CS had undergone a previous prosthetic dental implant(PI) (OR 12.4, 95% CI 4.0-38.1, p<0.001) or root canal treatment (RCT) (OR 2.43, 95% CI 1.12-5.26, p=0.025) more often than the healthy controls. The patients with CS and previous dental procedures had higher¹⁸FDG uptake in the LV myocardium (SUV max 8.6±3.3vs.5.5 ±1.8 (mean±SD), p<0.001) and mediastinal lymph nodes (9.3±4.6vs.5.4±1.7 (mean±SD), p<0.001) as compared to patients who did not undergo a dental procedure. The subset of CS patients with a previous PI or RCT had higher uptake levels in the myocardium (max SUV 9.4±3.1vs.6.7±2.0, p=0.011, number of abnormal LV Segments 10.3±3.1vs.6.5±2.8(mean±SD), p=0.008) and mediastinal lymph nodes(max SUV 10.5±4.8vs. 7.2±1.8,p=0.002) compared to those who underwent crowning or extraction. In addition, CS was diagnosed after a shorter latency period (47.3±21.0vs.81.6±25.3 months (mean±SD), p<0.001) following PI and RCT compared to other dental procedures.Conclusions:We observed a significant association between PI and RCT and the occurrence of CS. This group of patients also appear to have a more severe form of the disease.     

Impact of perioperative intravenous lidocaine infusion on postoperative pain and rapid recovery of patients undergoing gastrointestinal tumor surgery: a randomized,double-blind trial

BackgroundTo explore the effect of perioperative intravenous lidocaine infusion on postoperative pain and the rapid recovery of patients undergoing gastrointestinal tumor surgery.MethodsThe patients who underwent gastrointestinal tumor surgery from May to July 2020 were selected. The patients were randomly divided into the lidocaine group (group L) and control group (group C) by the random number table method, with 60 patients in each group. Both groups of patients received an intravenous drug infusion immediately after induction of tracheal intubation under general anesthesia. In group L, 1.5 mg/kg lidocaine was slowly injected intravenously at a rate of 1.5 mg·kg^–1·h^–1 to the surgical suture, and intravenous inhalation was used to maintain the depth of anesthesia. Group C patients were given the same volume of normal saline. The 2-, 4-, 7-, 14-, 30-, and 90-day numerical rating scale (NRS) and the proportion of chronic post-surgical pain (CPSP) after 3 months for both groups after surgery were recorded. Each patient’s postoperative comfort score, requiring analgesia, return of flatus, bowl movement, hospitalization days, hospitalization expenses, and adverse events were also recorded.ResultsOne hundred and twenty patients were enrolled but 5 of them failed to complete the treatment process. Therefore, 58 and 57 patients in group L and C were included into the final analysis. The NRS of patients in group L was significantly lower than that of group C at all time points after surgery (P<0.05), and the proportion of CPSP in group L was significantly lower than that of group C (P<0.05). The percentage of patients requiring analgesia and postoperative comfort score of group L was significantly higher than that of group C (P<0.01), patient’s return of flatus, bowl movement, hospitalization days, and hospitalization expenses in group L were significantly lower than those in group C (P<0.05). There were no difference of adverse events between the 2 groups (P>0.05).ConclusionsDuring the perioperative period of radical gastrointestinal tumor surgery, intravenous lidocaine infusion can reduce acute postoperative pain, promote postoperative gastrointestinal function recovery, and improve postoperative comfort.     

Homeopathic Treatment as an Add‐On Therapy May Improve Quality of Life and Prolong Survival in Patients with Non‐Small Cell Lung Cancer: A Prospective,Randomized, Placebo‐Controlled,Double‐Blind,Three‐Arm,Multicenter Study

Lessons Learned

• Conventional medicine and homeopathy work well together.
• Quality of life improves with additive homeopathy in patients with non‐small cell lung cancer (NSCLC).
• Survival improves with additive homeopathy in patients with NSCLC.

BackgroundPatients with advanced non‐small cell lung cancer (NSCLC) have limited treatment options. Alongside conventional anticancer treatment, additive homeopathy might help to alleviate side effects of conventional therapy. The aim of the present study was to investigate whether additive homeopathy might influence quality of life (QoL) and survival in patients with NSCLC.MethodsIn this prospective, randomized, placebo‐controlled, double‐blind, three‐arm, multicenter, phase III study, we evaluated the possible effects of additive homeopathic treatment compared with placebo in patients with stage IV NSCLC, with respect to QoL in the two randomized groups and survival time in all three groups. Treated patients visited the outpatients'' centers every 9 weeks: 150 patients with stage IV NSCLC were included in the study; 98 received either individualized homeopathic remedies (n = 51) or placebo (n = 47) in a double‐blinded fashion; and 52 control patients without any homeopathic treatment were observed for survival only. The constituents of the different homeopathic remedies were mainly of plant, mineral, or animal origin. The remedies were manufactured by stepwise dilution and succussion, thereby preparing stable Good Manufacturing Practice grade formulations.ResultsQoL as well as functional and symptom scales showed significant improvement in the homeopathy group when compared with placebo after 9 and 18 weeks of homeopathic treatment (p < .001). Median survival time was significantly longer in the homeopathy group (435 days) versus placebo (257 days; p = .010) as well as versus control (228 days; p < .001). Survival rate in the homeopathy group differed significantly from placebo (p = .020) and from control (p < .001).ConclusionQoL improved significantly in the homeopathy group compared with placebo. In addition, survival was significantly longer in the homeopathy group versus placebo and control. A higher QoL might have contributed to the prolonged survival. The study suggests that homeopathy positively influences not only QoL but also survival. Further studies including other tumor entities are warranted.     

Challenges and outcomes of a randomized study of early nutrition support during autologous stem-cell transplantation

Patients undergoing myeloablative conditioning regimens and autologous stem-cell transplantation (asct) are at high risk of malnutrition. This randomized study aimed to determine if early nutrition support (commenced when oral intake is less than 80% of estimated requirements) compared with usual care (commenced when oral intake is less than 50% of estimated requirements) reduces weight loss in well-nourished patients undergoing high-nutritional-risk conditioning chemotherapy and asct.In the 50 well-nourished patients who were randomized, the outcomes evaluated included changes in weight and lean body mass (mid-upper arm circumference), length of stay, time to hemopoietic engraftment, and quality of life (Memorial Symptom Assessment Scale – Short Form). On secondary analysis, after exclusion of a single extreme outlier, both groups demonstrated significant weight loss over time (p = 0.0005). Weight loss was less in the early nutrition support group at time of discharge (mean: −0.4% ± 2.9% vs. −3.4% ± 2.6% in the usual care group, p = 0.001). This difference in weight was no longer observed at 6 months after discharge (mean: −1.0% ± 6.8% vs. 1.4% ± 6.1%, p = 0.29).In practice, an early start to nutrition support proved difficult because of patient resistance and physician preference, with 8 patients (33%) in the control group and 4 (15%) in the intervention group not commencing nutrition support when stipulated by the study protocol. No significant differences between the groups were found for other outcomes. In well-nourished patients receiving asct, early nutrition support maintained weight during admission, but did not affect other outcomes. Interpretation of results should take into consideration the difficulties encountered with intervention implementation.