A Randomized Single-Blinded Study Comparing Preoperative with Post-Mastectomy PECS Block for Post-operative Pain Management in Bilateral Mastectomy with Immediate Reconstruction.

BACKGROUND: Ultrasound-guided pectoralis muscle blocks (PECS I/II) are well established for postoperative pain control after mastectomy with reconstruction. However, optimal timing is unclear. We conducted a randomized controlled single-blinded single-institution trial comparing outcomes of block performed pre-incision versus post-mastectomy. METHOD: Patients with breast cancer undergoing bilateral mastectomy with immediate expander/implant reconstruction were randomized to receive ultrasound-guided PECS I/II either pre-incision (PreM, n = 17) or post-mastectomy and before reconstruction (PostM, n = 17). The primary outcome was the average pain score using the Numerical Rating Score during post-anesthesia care unit (PACU) and inpatient stay, with the study powered to detect a difference in mean pain score of 2. Secondary outcomes included mean pain scores on postoperative day (POD) 2, 3, 7, 14, 90, and 180; pain catastrophizing scores; narcotic requirements; PACU/inpatient length of stay; block procedure time; and complications. RESULT: No significant differences between the two groups were noted in average pain score during PACU (p = 0.57) and 24-h inpatient stay (p = 0.33), in the 2 weeks after surgery at rest (p = 0.90) or during movement (p = 0.30), or at POD 90 and 180 at rest (p = 0.42) or during movement (p = 0.31). Median duration of block procedure (PreM 7 min versus PostM 6 min, p = 0.21) did not differ. Median PACU and inpatient length of stay were the same in each group. Inpatient narcotic requirements were similar, as were length of stay and post-surgical complication rates. CONCLUSION: Intraoperative ultrasound-guided PECS I/II block administered by surgeons following mastectomy had similar outcomes to preoperative blocks. TRIAL REGISTRATION: This trial is registered with Clinical Research Information Service (NCT03653988).

Dosimetric analysis of a compartmental model for radioligand uptake in tumor lesions.

Radioligand therapy is a targeted cancer therapy that delivers radiation to tumor cells based on the expression of specific markers on the cell surface. It has become an important treatment option in metastasized neuroendocrine tumors and advanced prostate cancer. The analysis of absorbed doses in radioligand therapies has gained much attention and remains a challenging task due to individual pharmacokinetics. As an alternative to the often used sum of exponential functions in intra-therapeutic dosimetry, a basic compartmental model for the pharmacokinetics of radioligands is described and analyzed in this paper. In its simplest version, the model behavior is determined by the uptake capacity and the association constant and can be solved analytically. The model is extended with rates for excretion from the source compartment and externalization from the lesion compartment. Numerical calculations offer an insight into the quantitative effects of the model parameters on the absorbed dose in the tumor lesion. This analysis helps understanding the importance of clinically relevant factors, e.g. the effect on absorbed doses of modified radioligands that bind to albumin. Using clinical data, the potential application in intra-therapeutic dosimetry is illustrated and compared to the bi-exponential function which lacks a mechanistical basis. While the compartmental model is found to constitute a feasible alternative in these examples, this has to be confirmed by further clinical studies.

[Diagnosis and treatment of malignant mesothelioma of the tunica vaginalis testis: a series of 7 cases].

Objective: To investigate the clinical features, diagnosis, prognosis of malignant mesothelioma of the tunica vaginalis testis (MMTVT). Methods: The clinicopathological data of 7 patients with MMTVT who treated at Sun Yat-sen University Cancer Center between January 2010 and October 2022 were retrospectively reviewed. Cases were first diagnosed at (M (IQR)) 49 (23) years old (range: 27 to 64 years old). The main clinical manifestations were scrotal enlargement (7 cases) and hydrocele (2 cases). Results: Three patients underwent radical orchiectomy as initial treatment, 2 cases underwent hydrocelectomy due to diagnosis of hydrocele, followed by radical orchiectomy at Sun Yat-sen University Cancer Center, and 2 cases underwent transscrotal orchiectomy. Common tumor markers of testicular cancer were not significantly elevated in MMTVT. The expression of tumor PD-L1 was positive in 2 out of the 3 cases. One patient received adjuvant chemotherapy and 2 patients received first-line chemotherapy after tumor recurrence. Chemotherapy regimens used include cisplatin+pemetrexed. Up to October 2022, 3 cases relapsed, of which 2 cases died. The median overall survival was 35 months (range: 4 to 87 months) and the median progression-free survival was 6 months (range: 2 to 87 months). Conclusions: MMTVT at early stage should be treated with early radical orchiectomy and followed up closely after surgery. The cisplatin+pemetrexed regimen is a common option for the treatment of metastatic MMTVT, while whether immune checkpoint inhibitors could serve as a second-line treatment option deserves further research.

[Value of thyroid 99mTcO4- imaging ROI ratio for estimating 131I dose in individualized treatment of hyperthyroidism].

OBJECTIVE: To investigate the feasibility of using thyroid 99mTcO4- imaging ROI ratio instead of 24 h radioactive iodine uptake (RAIU) for estimating 131I dose in individualized treatment of hyperthyroidism. METHODS: We retrospectively analyzed the clinical data of 132 patients receiving 131I treatment in our department between January and June, 2019. According to their 3 h/24 h RAIU peak ratio, the patients were divided into peak forward (≥80%) group and no peak forward (< 80%) group. In the former group, the therapeutic 131I dose was calculated based the Marinelli formula (131I dose=thyroid mass×planned amount/24 h RAIU), and in the latter group, the correlation between the ROI ratio and the 24 h RAIU was analyzed, and the 131I dose was calculated using a modified Marinelli formula where 24 h RAIU was replaced by a converted ROI ratio. The two groups of patients were compared for antithyroid drug type and discontinuation time, thyroid hormones and related antibodies, thyroid area, thyroid mass and 131I dose. All the patients were and followed up for one year to analyze the treatment efficacy. The ROI ratios after the treatment were analyzed in the two groups using ROC curves. RESULTS: There was a significant positive correlation between the ROI ratio and 24 h RAUI in the no peak forward group (Y=58.13 + 0.2X, R2=0.118, P < 0.05), and the formula for calculating 131I dose was converted into: 131I dose=thyroid mass× planned amount/(58.13+0.2×ROI ratio)%. Before the treatment, therapeutic 131I dose, thyroid hormone levels, TRAb, 3 h and 24 h RAIU, thyroid area, thyroid mass, and ROI ratio all differed significantly between the two groups (P < 0.05). At 3 months after treatment, thyroid hormone levels, TRAb, TPOAb, thyroid area, thyroid mass, ROI ratio, response rate, hypothyroidism rate, cure rate, remission rate, and nonresponse rate were similar between two groups (P>0.05). At the 1-year follow-up, the composition ratios of hyperthyroidism, hypothyroidism and cured cases remained similar between two groups (P>0.05). ROC curve analysis showed that at 3 months after treatment, the optimal cutoff values of ROI ratio for predicting hyperthyroid recurrence and hypothyroidism were 15.79 and 6.33, respectively. CONCLUSION: Thyroid 99mTcO4- imaging ROI ratio can be used for calculating 131I dose in individualized treatment of hyperthyroidism and for prognostic evaluation of the patients.

[Suppression of HMGB1 inhibits neuronal autophagy and apoptosis to improve neurological deficits in rats following intracerebral hemorrhage].

OBJECTIVE: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats. METHODS: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 µL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA. RESULTS: The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05). CONCLUSION: Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.

[Investigating the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of severe scald rabbits based on 16S ribosomal RNA high-throughput sequencing].

Objective: To investigate the effects of Modified Sijunzi Decoction on the diversity of intestinal microflora of in severe scald rabbits based on 16S ribosomal RNA (16S rRNA) high-throughput sequencing. Methods: The experimental research method was adopted. Ninety Japanese big-ear rabbits regardless gender, aged 6 to 8 months, were randomly divided into normal control group, scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group, with 18 rabbits in each group. The rabbits in normal control group were free to eat and drink, and the rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group were intragastrically administered normal saline, 0.2 g/mL Modified Sijunzi Decoction, 1.0 g/mL Modified Sijunzi Decoction, and 5.0 g/mL Modified Sijunzi Decoction, respectively for 7 days after sustaining full-thickness scalding of 30% total body surface area. On the 1st, 3rd, and 7th day after grouping, the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and IL-10 in ileal mucosa tissue of rabbits in each group were determined by enzyme-linked immunosorbent assay, and the number of samples in each group at each time point was 6. According to the above experimental results, another 9 rabbits were selected and divided into normal control group, scald alone group and scald+medium-dose group, with 3 rabbits in each group. The grouping and treatment methods of rabbits in each group were the same as before. On the 7th day after grouping, the V3, V4 region of 16S rRNA of ileum mucosa of rabbits in three groups were sequenced by high-throughput sequencing technology. The number of quality bacteria was counted by QIME software. The classifications of phylum, class, order, family and genus of microflora were analyzed by RDP Classifier software. The α diversity (Ace, Chao1, Simpson, and Shannon indexes) and ß diversity were analyzed by Illumina MiSeq sequencing technology, and the number of experiment samples in each group was 3. Data were statistically analyzed with analysis for variance of factorial design, SNK test, and Bonferroni correction. Results: Compared with that in normal control group, the levels of TNF-α of ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping and scald+medium-dose group on the 1st and 3rd day after grouping were all significantly increased (P<0.01), the levels of IL-1ß in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01). Compared with that in scald alone group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping, and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 3rd and 7th day after grouping and scald+medium-dose group on the 1st day after grouping were all significantly decreased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+low-dose group on the 7th day after grouping and scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and scald+high-dose group on the 3rd and 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald+low-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in medium-dose scald alone group on the 1st, 3rd, and 7th day after grouping and in high-dose scald alone group on the 3rd and 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+medium-dose group on the 1st, 3rd, and 7th day after grouping and in scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01). Compared with that in scald medium-dose group, the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald+high-dose group on the 1st, 3rd, and 7th day after grouping were all significantly decreased (P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald+high-dose group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 1st day after grouping, the levels of TNF-α in ileal mucosa tissue of rabbits in scald alone group on the 3rd and 7th day after grouping and in normal control group on the 3rd day after grouping were all significantly increased (P<0.05 or P<0.01), and the levels of IL-1ß in ileal mucosa tissue of rabbits in scald alone group both on the 3rd and 7th day after grouping were significantly increased (P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in both scald+low-dose group and scald+high-dose group on the 7th day after grouping and scald+medium-dose group both on the 3rd and 7th day after grouping were significantly increased (P<0.05 or P<0.01), and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+high-dose group on the 3rd and 7th day after grouping and in scald+medium-dose group on the 7th day after grouping were all significantly decreased (P<0.05 or P<0.01), and the level of IL-1ß in ileal mucosa tissue of rabbits in scald+medium-dose group on the 7th day after grouping was significantly decreased (P<0.01), and the level of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). Compared with that on the 3rd day after grouping, the levels of TNF-α and IL-1ß in ileal mucosa tissue of rabbits in scald alone group and the levels of IL-10 in ileal mucosa tissue of rabbits in normal control group, scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly increased (P<0.05 or P<0.01); and the levels of TNF-α in ileal mucosa tissue of rabbits in scald+low-dose group, scald+medium-dose group, and scald+high-dose group on the 7th day after grouping were all significantly decreased (P<0.05), and the levels of IL-1ß in ileal mucosa tissue of rabbits both in scald+medium-dose group and scald+high-dose group on the 7th day after grouping were significantly decreased (P<0.05 or P<0.01), and the levels of IL-10 in ileal mucosa tissue of rabbits in scald alone group on the 7th day after grouping was significantly decreased (P<0.01). On the 7th day after grouping, the high-quality sequences obtained from the microflora in ileum mucosa of rabbits in normal control group, scald alone group, and scald+medium-dose group were 96 023, 107 365, and 95 921, respectively. At the classification level of phylum, class, order, family, and genus of the microflora in ileum mucosa of rabbits in three groups were all Bacteroidetes and Firmicutes, Clostridium and Bacteroidetes, Clostridium and Bacteroidetes, Rumenobacteriaceae and Clostridium and Bacteroideaceae, Clostridium and Bacteroidetes and rumen bacteria mainly, while the percentage of microflora in each group was different. There were no significant differences in Ace, Chao1, Simpson, Shannon indices (P>0.05), and no obvious difference in ß diversity of microflora in ileal mucosa tissue of rabbits among three groups. Conclusions: After severe scalding, the inflammatory response of rabbit ileal mucosa tissue is obvious and increased in a time-dependent manner. Modified Sijunzi Decoction can reduce inflammation with optimal therapeutic concentration of 1.0 g/mL. The technology of high-throughput sequencing can reflect the structural composition of the intestinal microflora accurately. The ileal microflora of the severe scald rabbit can be regulated by the administration of Modified Sijunzi Decoction.

Yeast cell wall upregulated cell-mediated immune responses to Newcastle disease virus vaccine.

A recent study has suggested that yeast cell wall product (YP) enhanced serum hemagglutination inhibition (HI) titers and intestinal sIgA responses in chickens immunized with Newcastle disease virus (NDV) vaccine. In the present study, the cell-mediated immune responses elicited by NDV and YP were investigated in commercial broilers. Broilers were fed 0 or 0.1% YP and immunized with a live NDV vaccine via an intraocular-and-intranasal route at 14 and 28 days old. After that, blood samples were collected for determination of HI titer, cytokine content, and blood analysis. Eight chickens were randomly selected from each group and sacrificed. Lymphocytes were harvested from the spleens for lymphocyte proliferation and flow cytometry analysis. Total RNA was extracted from spleen and jejunum for RT-qPCR analysis. The results showed that YP significantly increased serum concentration of IL-4, IL-6, IFN-γ, TNF-ß, as well as promoted lymphocytes proliferation in broilers immunized with NDV vaccine. The enhanced cell-mediated immunity is correlated with the upregulated mRNA expression of TGF-ß, IL-6, TLR5, GATA-3, and T-bet in the spleen and upregulated mRNA expression of CCR-9, J-chain, pIgR, and TLR3 in the jejunum of chickens. It is noteworthy that no significant side effect was observed after the administration of YP. Therefore, YP could be safely used as potential immunopotentiator assisting NDV vaccine for chickens.

[Preoperative diagnostic value of 99mTc- MIBI SPECT/CT imaging combined with semiquantitative analysis in hyperparathyroidism and factors affecting its efficacy].

OBJECTIVE: To evaluate the diagnostic efficacy of technetium-99m methoxyisobutylisonitrile single photon emission/ computed tomography (99mTc- MIBI SPECT/CT), 99mTc- MIBI double- phase scintigraphy (DPS) DPS and ultrasound (US) in preoperative localization of hyperparathyroidism (HPT) and explore the factors affecting the diagnostic efficacy of 99mTc-MIBI SPECT/CT. METHODS: We retrospectively analyzed the data of 104 patients with HPT undergoing surgical resection between January, 2015 and July, 2019. Preoperative 99mTc-MIBI imaging was performed in all the patients, and 82 patients also received US examination preoperatively. Semi-quantitative analysis was used to draw the region of interest and calculate the lesion/ ipsilateral deltoid muscle (T/NT) uptake ratio. The sensitivity and detection performance of 99mTc-MIBI SPECT/CT, DPS and US in the diagnosis of HPT patients were compared, and the correlations of the T/NT ratios of parathyroid adenoma (PA) and parathyroid hyperplasia (PH) with the expression levels of COX-2 and Bcl-2 were analyzed. RESULTS: The diagnostic sensitivity of 99mTc- MIBI SPECT/CT, DPS and US for HPT was 95.19% (99/104), 91.3% (95/104) and 81.71% (67/82), respectively, demonstrating a significantly higher diagnostic sensitivity of 99mTc-MIBI SPECT/CT than US (χ2=9.59, P=0.008). For PH lesions, 99mTc-MIBI SPECT/CT had the highest diagnostic sensitivity, followed by DPS and then by US (P < 0.05), but their sensitivity did not differ significantly for PA (P>0.05). The T/NT ratio in fatty hyperplastic glands was significantly lower than that in fat-free hyperplastic glands (P=0.009). In PA, Bcl-2 expression was significantly lower in false negative lesions than in true positive lesions (P=0.046), but Cox-2 expression did not show such a difference (P>0.05). In PH lesions, the expressions of Bcl-2 and Cox- 2 did not differ significantly between false negative than true positive lesions (P>0.05). CONCLUSIONS: 99mTc-MIBI SPECT/CT has a high sensitivity for HPT localization, and the T/NT ratio is positively correlated with the lesion volume. An increased expression of Bcl-2 in PA lesions and a decreased cell fat content in PH lesions can facilitate the detection of HPT glands by 99mTc-MIBI SPECT/CT.

[Interpretation of the American Association for Thoracic Surgery expert consensus document: coronary artery bypass grafting in patients with ischemic cardiomyopathy and heart failure in 2021].

An expert consensus on coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM) was released by the American Association for Thoracic Surgery in May 2021, which contains a vast array of perioperative recommendations. During preoperative period, a comprehensive assessment on ICM including myocardial viability and valve function by a multi-disciplinary team (MDT) approach should be performed. In terms of intraoperative period, multiple arterial conduits and on-pump CABG using cold blood cardioplegia should be considered, meanwhile, other aspects involving concomitant management of mitral valve regurgitation and arrythmia, as well as active use of mechanical cardiac assist devices (e.g., intra-aortic balloon pump) should also be achieved. Finally, a range of postoperative interventions which includes standardized MDT management in intensive care unit (ICU), continuous use of cardiac assist devices, cardiac pacing, close follow-up within 90 days and drug treatment strictly guided by the guidelines after discharge from hospital should be conducted. The above-mentioned perioperative bundled care might reduce perioperative complications and operative mortality, and thus improve the prognosis of the patients with ICM.

[Eltrombopag for thrombocytopenia in 24 children after hematopoietic stem cell transplantation].

Objective: To evaluate the efficacy and safety of eltrombopag for children with thrombocytopenia after hematopoietic stem cell transplantation (HSCT). Methods: Clinical data of 24 patients with thrombocytopenia after HSCT,who were treated with eltrombopag in the Department of Pediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from August 1, 2018 to April 1, 2019 were analyzed retrospectively. The response rate and adverse reactions of eltrombopag were evaluated. Patients were divided into groups by source of hematopoietic stem cells (umbilical cord blood group and peripheral stem cell group) and type of disease (malignant and non-malignant disease group) and the clinical outcomes between groups were compared. Rank Sum test was used for comparisons between groups. Results: Among 24 cases, 15 were males and 9 females, the age of starting eltrombopag was 7.7 (2.6-13.7) years, the time of eltrombopag treatment after HSCT was 27.5 (8.0-125.0) days, the time from treatment to complete response (CR) was 23.5 (6.0-83.0) days, with the treatment course 36.5 (8.0-90.0) days. The total dose of eltrombopag was 1 400(200-5 900) mg. Complete response rate was 92% (22/24),without eltrombopag related adverse reactions. Comparing with peripheral stem cell group (n=8), the course and total dose of eltrombopag in umbilical cord blood group (n=16) were significantly reduced(24.5 (8.0-81.0) vs. 65.5 (35.0-90.0) d, Z=-3.004, P=0.002; 900.0 (200.0-3 850.0) vs. 2 862.5 (1 175.0-5 900.0) mg, Z=-2.604, P=0.007), but no significant differences were found in the time from treatment to complete response, platelet count after 2 weeks of eltrombopag withdrawal or platelet count at the end point of follow-up (all P>0.05). Comparing malignant patients (n=12) and non-malignant patients (n=12), no significant differences were found in the time from treatment to complete response, course, total dose, platelet count after 2 weeks of eltrombopag withdrawal, and platelet count at the end point of follow-up in non-malignant patients (all P>0.05). Conclusion: Eltrombopag is safe and maybe effective for thrombocytopenia after HSCT, especially for umbilical cord blood transplantation.

Effect of dermatological consultation on survival in patients with checkpoint inhibitor-associated cutaneous toxicity.

BACKGROUND: Cutaneous immune-related adverse events (cirAEs) are a common side-effect of immune checkpoint inhibitors (ICIs). However, prior work examining these toxicities in detail has considered only the fraction of events evaluated by dermatologists. Associations between dermatology referral, cirAE treatment and survival outcomes remain underexplored across care settings. OBJECTIVES: To comprehensively categorize cirAE patterns among all patients treated with immunotherapy at our institution, and to evaluate: (i) the effect of dermatology referral on cirAE treatment and (ii) the impact of cirAE treatment on survival. METHODS: This was a retrospective cohort analysis of patients with cancer who initiated ICI therapy between 1 January 2016 and 8 March 2019 and developed one or more cirAEs, as screened for using International Classification of Diseases 10th revision codes and confirmed via manual chart review (n = 358). All relevant information documented prior to 31 March 2020 was included. RESULTS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred (odds ratio 6·08, P < 0·001). Patients who received any cirAE treatment had improved progression-free survival [hazard ratio (HR) 0·59, P = 0·001] and overall survival (HR 0·58, P = 0·007) compared with those who did not. CONCLUSIONS: CirAEs evaluated by dermatologists were significantly more likely to be treated than cirAEs that were not referred, and patients who received any treatment for a cirAE had improved survival outcomes.

Carcinogenesis of Male Oral Submucous Fibrosis Alters Salivary Microbiomes.

Most oral squamous cell carcinoma (OSCC) tumors arise from oral premalignant lesions. Oral submucous fibrosis (OSF), usually occurring in male chewers of betel quid, is a premalignant stromal disease characterized by a high malignant transformation rate and high prevalence. Although a relationship between the inhabited microbiome and carcinogenesis has been proposed, no detailed information regarding the oral microbiome of patients with OSF exists; the changes of the salivary microbiome during cancer formation remain unclear. This study compared the salivary microbiomes of male patients with OSCC and a predisposing OSF background (OSCC-OSF group) and those with OSF only (OSF group). The results of high-throughput sequencing of the bacterial 16S rRNA gene indicated that OSF-related carcinogenesis and smoking status significantly contributed to phylogenetic composition variations in the salivary microbiome, leading to considerable reductions in species richness and phylogenetic diversity. The microbiome profile of OSF-related malignancy was associated with increased microbial stochastic fluctuation, which dominated the salivary microbiome assembly and caused species co-occurrence network collapse. Artificial intelligence selection algorithms consistently identified 5 key species in the OSCC-OSF group: Porphyromonas catoniae, Prevotella multisaccharivorax, Prevotella sp. HMT-300, Mitsuokella sp. HMT-131, and Treponema sp. HMT-927. Robust accuracy in predicting oral carcinogenesis was obtained with our exploratory and validation data sets. In functional analysis, the microbiome of the OSCC-OSF group had greater potential for S-adenosyl-l-methionine and norspermidine synthesis but lower potential for l-ornithine and pyrimidine deoxyribonucleotide synthesis and formaldehyde metabolism. These findings indicated that the salivary microbiome plays important roles in modulating microbial metabolites during oral carcinogenesis. In conclusion, our results provided new insights into salivary microbiome alterations during the malignant transformation of OSF.

[Effects of preoperative segmental mobility on the clinical and radiographic outcomes following one-level artificial cervical disc replacement].

Objective: To investigate the effects of preoperative segmental range of motion (ROM) on clinical and radiographical outcomes after artificial cervical disc replacement (ACDR) and explore whether ACDR could be indicated for patients with preoperative limited or excessive segmental ROM. Methods: From January 2008 to December 2017, patients who underwent Prestige-LP ACDR in West China Hospital were retrospectively reviewed. The preoperative and postoperative X-rays of the cervical spine were collected to measure the radiographic parameters, including cervical lordosis (CL), C(2-7) ROM, disc height (DH), disc angle (DA) and ROM at the arthroplasty level. Clinical outcomes were evaluated using the Japanese Orthopedic Association (JOA) and the Neck Disability Index (NDI) scores. The correlation between preoperative segmental ROM and postoperative clinical and radiographical outcomes were also analyzed. Results: A total of 161 patients were analyzed, with 73 males and 88 females. The mean age was (44±8) years, and the follow-up period was 34 months (12-120 months). JOA and NDI scores improved after ACDR (P<0.05). However, postoperative C(2-7) ROM and ROM at the arthroplasty level were comparable with preoperative counterparts (both P>0.05). Preoperative segmental ROM positively correlated with C(2-7) ROM and ROM at the arthroplasty segment (r=0.213、0.271, both P<0.05), but was negatively correlated with the change of ROM (r=-0.534, P<0.05). The segmental ROM was 4.0°±1.0° in the limited-ROM group (A) and 14.6°±1.3° in the excessive-ROM group (B), respectively. There were significantly more patients diagnosed with cervical spondylosis in group A than in group B (35.5% vs 10.7%, P<0.05). The level-distribution was statistically different between the two groups. C(5/6) and C(6/7) were prone to limited motion in group A, while C(4/5) and C(5/6) were predisposed to excessive motion in group B (all P<0.05). After surgery, C(2-7) ROM increased for 14.2°±16.8° in group A, while paradoxically decreased for 2.2°±14.4° in group B. However, C(2-7) ROM in group B was still larger than that in group A (P<0.05). Similarly, the ROM at the arthroplasty level increased by 3.1°±3.7° in group A, whereas the values decreased by 4.4°±4.2° in group B postoperatively. In addition, group A still had less segmental ROM than group B (P<0.05). The preoperative DH in group A was less than that in group B (P<0.05). The rates of ASD, HO, and high-grade HO in group A were all higher than those in group B but without significant differences (all P>0.05). Conclusion: Preoperative segmental ROM has no significant effects on clinical outcomes after ACDR; it has a positive correlation with postoperative global and segmental ROM while is negatively correlated with ROM change.

Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Over-expression of DJ-1 attenuates effects of curcumin on colorectal cancer cell proliferation and apoptosis, by H. Shang, T. Wang, F. Shang, M. Li, Y. Luo, K.-M. Huang, published in Eur Rev Med Pharmacol Sci 2019; 23 (7): 3080-3087-DOI: 10.26355/eurrev_201904_17591-PMID: 31002157" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17591.

Prognosis and clinicopathologic features in patients with gastric stump cancer after curative surgery.

Background: Gastric stump ("remnant") cancer is the development of a malignancy related to previous gastric surgery. Prognosis in gastric stump cancer, compared with that in primary gastric cancer, is still controversial. Methods: From January 1988 to December 2012 at a single medical centre in Taiwan, 105 patients with gastric stump cancer, including 85 with previous peptic ulcer disease and 20 with previous gastric cancer, were analyzed for clinicopathologic characteristics and overall survival (os). Results: The 5-year os rates for patients with gastric stump cancer and with primary gastric cancer were 51.2% and 54.5% respectively (p = 0.035). Analysis of clinicopathologic characteristics indicated that, compared with patients having primary gastric cancer, those with gastric stump cancer had more lymph node metastasis (p < 0.001) and had been diagnosed at a more advanced stage (p = 0.047). Multivariate analysis with os as an endpoint showed that age [p = 0.015; hazard ratio (hr): 2.300; 95% confidence interval (ci): 1.173 to 4.509], tumour size (p = 0.037; hr: 1.700; 95% ci: 1.031 to 2.801), stromal reaction (p = 0.021; hr: 1.802; 95% ci: 1.094 to 2.969), and pathologic N category (p = 0.001; hr: 1.449; 95% ci: 1.161 to 1.807) were independent predictors in gastric stump cancer. The os rates for patients with gastric stump cancer who previously had gastric cancer or peptic ulcer disease were 72.9% and 50.0% respectively (p = 0.019). The Borrmann classification was more superficial (p = 0.005), lymph node metastases were fewer (p = 0.004), and staging was less advanced (p = 0.025) in patients with gastric stump cancer who previously had gastric cancer than in their counterparts who previously had peptic ulcer disease. Conclusions: Survival is poorer in patients with gastric stump cancer who previously had peptic ulcer disease than in those who previously had primary gastric cancer. Patients with gastric stump cancer who previously had gastric cancer and could receive curative gastrectomy tended to have a better prognosis because of a more superficial Borrmann classification. Regular follow-up in patients who have undergone gastric surgery is recommended for the early detection of gastric stump cancer.

Long noncoding RNA DARS-AS1 acts as an oncogene by targeting miR-532-3p in ovarian cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA DARS-AS1 acts as an oncogene by targeting miR-532-3p in ovarian cancer, by K. Huang, W.-S. Fan, X.-Y. Fu, Y.-L. Li, Y.-G. Meng, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2353-2359. DOI: 10.26355/eurrev_201903_17379. PMID: 30964159" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17379.

Overexpression of XIST facilitates cell proliferation, invasion and suppresses cell apoptosis by reducing radio-sensitivity of glioma cells via miR-329-3p/CREB1 axis.

OBJECTIVE: Glioma is a malignant brain cancer capable of spreading to the microenvironment. Long non-coding RNA (lncRNA) X inactive specific transcript (XIST) was recognized as a significant regulator in many cancers. However, the molecular mechanism of XIST in glioma cell radio-sensitivity requires further exploration. PATIENTS AND METHODS: The expression of XIST, microRNA (miR)-329-3p and cyclic AMP response element-binding protein 1 (CREB1) was evaluated by quantitative Real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry, respectively. Transwell assay was performed to detect cell invasion. Protein expression of gamma-H2AX (γ-H2AX) and CREB1 was determined by Western blot. The correlation between miR-329-3p and XIST or CREB1 was determined by dual-luciferase reporter assay. Animal models were established by subcutaneously injecting U251 cells transfected with sh-XIST and sh-NC. RESULTS: XIST and CREB1 were overexpressed whereas miR-329-3p was low-expressed in glioma tumors and cells compared with the normal counterparts. XIST knockdown inhibited cell proliferation, invasion and induced cell apoptosis by enhancing cell sensitivity to X-ray radiation in glioma. Then, we discovered that miR-329-3p directly interacted with XIST or CREB1 in glioma. In addition, miR-329-3p inhibitor abolished XIST silencing-induced regulatory effects on cell proliferation, apoptosis, invasion, and radio-sensitivity. Meanwhile, miR-329-3p inhibitor counteracted CREB1 silencing-induced inhibition on cell progression and facilitation on radio-sensitivity in glioma. Moreover, we found that XIST could increase CREB1 expression by sponging miR-329-3p. Animal experiments revealed that XIST silencing restrained tumor growth in vivo. CONCLUSIONS: XIST accelerates cell proliferation, invasion and inhibits cell apoptosis by repressing radio-sensitivity of glioma via enhancing CREB1 expression through sponging miR-329-3p, representing prospective methods for glioma treatment.