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The Impact of Prior Salvage Treatment With Immune Checkpoint Inhibitors on Hodgkin Lymphoma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Single-Center Experience

Clin Lymphoma Myeloma Leuk. 2021 May 19:S2152-2650(21)00193-2. doi: 10.1016/j.clml.2021.05.006. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of the study was to assess the impact of the previous use of immune-checkpoint inhibitors (ICIs) on the clinical course of Hodgkin Lymphoma (HL) patients undergoing autologous hematopoietic stem cell transplantation (ASCT).

METHODS: A single-center, retrospective chart review of adult HL patients who received ASCT from January 1, 2014, to December 31, 2019, was conducted. Primary endpoints included the length of stay (LOS) and the composite outcome of late-onset noninfectious fever (LONIF) or late-onset hypotension (LOH) requiring intravenous fluid (IVF) resuscitation. Secondary endpoints included number of days until neutrophil engraftment, documented infections, and corticosteroid use.

RESULTS: A total of 52 HL patients were included. Nine (17%) received ICI before ASCT, and 43 (83%) patients underwent standard salvage chemotherapy. The composite outcome of LONIF or LOH requiring IVF resuscitation was significantly higher in patients previously treated with ICIs compared with those who received standard non-ICI salvage chemotherapy (78% vs. 33%; P = .022). The differences between the median LOS and time to neutrophil engraftment were not statistically significant (P = .94 and P = .083, respectively). All LONIF patients received systemic corticosteroids with symptom resolution.

CONCLUSION: The composite outcome of LONIF or LOH requiring IVF resuscitation was significantly higher in patients who received prior ICI salvage therapy. LOS and time to neutrophil engraftment were not affected by prior ICI therapy. Early institution of steroids may prevent the evolution of additional sequelae associated with engraftment or engraftment-like syndrome that can complicate ASCT.

PMID:34158267 | DOI:10.1016/j.clml.2021.05.006

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Patient education improves pain and function in people with knee osteoarthritis with better effects when combined with exercise therapy: a systematic review

J Physiother. 2021 Jun 19:S1836-9553(21)00054-0. doi: 10.1016/j.jphys.2021.06.011. Online ahead of print.

ABSTRACT

QUESTION: Is patient education effective as a standalone intervention or combined with other interventions for people with knee osteoarthritis?

DESIGN: Systematic review of randomised controlled trials. MEDLINE, EMBASE, SPORTDiscus, CINAHL and Web of Science were searched from inception to April 2020. The Cochrane Risk of Bias tool was used for included studies, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to interpret certainty of results.

PARTICIPANTS: People with knee osteoarthritis.

INTERVENTION: Any patient education intervention compared with any non-pharmacological comparator.

OUTCOME MEASURES: Primary outcomes were self-reported pain and function.

RESULTS: Twenty-nine trials involving 4,107 participants were included, informing low to very-low certainty evidence. Nineteen of 28 (68%) pooled comparisons were not statistically significant. Patient education was superior to usual care for pain (SMD -0.35, 95% CI -0.56 to -0.14) and function in the short term (-0.31, 95% CI -0.62 to 0.00), but inferior to exercise therapy for pain in the short term (0.77, 95% CI 0.07 to 1.47). Combining patient education with exercise therapy produced superior outcomes compared with patient education alone for pain in the short term (0.44, 95% CI 0.19 to 0.69) and function in the short (0.81, 95% CI 0.54 to 1.08) and medium term (0.39, 95% CI 0.15 to 0.62). When using the Western Ontario and McMaster Universities Osteoarthritis Index for these comparisons, clinically important differences indicated that patient education was inferior to exercise therapy for pain in the short term (MD 1.56, 95% CI 0.14 to 2.98) and the combination of patient education and exercise therapy for function in the short term (8.94, 95% CI 6.05 to 11.82).

CONCLUSION: Although patient education produced statistically superior short-term pain and function outcomes compared with usual care, differences were small and may not be clinically important. Patient education should not be provided as a standalone treatment and should be combined with exercise therapy to provide statistically superior and clinically important short-term improvements in function compared with education alone.

REGISTRATION: PROSPERO CRD42019122004.

PMID:34158270 | DOI:10.1016/j.jphys.2021.06.011

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Botulinum toxin type a intralesional monotherapy for treating human hypertrophic scar in a dose-dependent manner: In an animal model

J Plast Reconstr Aesthet Surg. 2021 Apr 24:S1748-6815(21)00153-4. doi: 10.1016/j.bjps.2021.03.062. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of Botulinum toxin type A (BTX-A) in treating or preventing a hypertrophic scar (HS) had been reported in clinical studies. However, the dose-effect relationship remains unclear.

OBJECTIVE: To study the dose-effect relationship of BTX-A intralesional monotherapy treating human HS.

METHODS: Six HS tissues were collected from six patients. Each tissue was segmented into 24 specimens and split into four groups: negative control (group A), 0.5U BTX-A (group B), 1U BTX-A (group C), and 2U BTX-A (group D). Six nude mice, each was prepared by implanting four specimens (one from each group) into the back for a total of 24 specimens. The process mentioned above were repeated six times. A re-entry operation was performed to obtain the specimens after 8 weeks. The weight of HS, the expression of decorin and TGF-β1, the proliferation, and migration ability of hypertrophic scar fibroblasts (HSFBs) were compared among groups.

RESULTS: The weight of HS, the expression of decorin and TGF-β1, the proliferation, and migration ability of HSFBs showed significant differences in groups C and D as compared to group A; there has been no statistical significance in group B.

CONCLUSION: BTX-A showed significant therapeutic efficacy when compared with the negative control group in a dose-dependent manner. BTX-A can reduce the weight of HS, upregulate the expression of decorin, downregulate the expression of TGF-β1, and inhibit HSFBs proliferation and migration ability. This study indicates that BTX-A intralesional monotherapy treating HS should reach a threshold dose to achieve an effective treatment, and a high dose of BTX-A is more effective than a low dose.

PMID:34158272 | DOI:10.1016/j.bjps.2021.03.062

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Posterior urethral valves and the risk of neurodevelopmental disorders in two FINNISH cohorts

J Pediatr Urol. 2021 Jun 5:S1477-5131(21)00298-9. doi: 10.1016/j.jpurol.2021.05.027. Online ahead of print.

ABSTRACT

BACKGROUND: The Posterior Urethral Valve (PUV) is a persistent membrane of the urethra, which causes obstruction in the urogenital tract in boys. To our knowledge, no comprehensive reports have been published on whether PUV is associated to neurodevelopmental disorders. Here, we analyzed a cohort of PUV patients for neurodevelopmental disorders and verified findings in an older cohort.

METHODS: In a register based study, we reviewed the hospital registries for patients treated for PUV during 1992-2013 to identify those with neurodevelopmental disorders. Primary outcome measure was any neurodevelopmental diagnosis. Secondary outcome measures were specific disorders: ASD; ADHD, intellectual disability, learning disabilities. Birth weight and gestational age were recorded, serum creatinine levels at specific timepoints were noted. We then investigated these variables to see any correlations to neurodevelopmental disorders. We replicated the strategy for verification in an older cohort of PUV-patients, who had been treated in our institute during 1970-1991.

RESULTS: We identified 87 patients treated for PUV of which thirteen (15%) had a verified diagnosis of a neurodevelopmental disorder. 2.3% of PUV patients fulfilled criteria of mild intellectual disability (F70.0/F79.0), 9% had ADHD/ADD-spectrum diagnoses (F90.0/F90.9) and 2.3% had learning disabilities (F83/F81.3). 5.7% of patients presented with difficulties in social interactions (F93.89, F94.8). Five patients presented with more than one neurodevelopmental diagnosis. We confirmed these findings in the older cohort of patients, where a verified neurodevelopmental diagnosis was detected in 14% of patients. We identified no statistically significant associations to gestational age, birth weight or creatinine levels of PUV-patients with neurodevelopmental diagnoses as compared to the PUV-patients not diagnosed for neurodevelopmental disorders. Intellectual disability/mental retardation was more prevalent in our material and this association was statistically significant.

DISCUSSION: We show, that the prevalence of intellectual disability among PUV patients exceeds the cumulative prevalence in Finland in both cohorts analyzed here. 15% of PUV-patients presented with a diagnosis of a neurodevelopmental disorder. To our knowledge, this is the first study attempting to outline neurodevelopmental disorders among boys with PUV. This study has limitations. It is register based and only diagnoses made at an institute within our hospital district are considered. The PUV-patients may be under closer surveillance than age-matched healthy children, which may lead to an overrepresentation of cases. The patient number is small and the small subsets of patients within each cohort hamper any further statistical analysis. The neurodevelopmental impacts of pediatric general anesthesia remain elusive and may have corollaries which must be kept in mind when interpretating our results. Patients with PUV require close follow-up in a multi-disciplinary manner, not forgetting neurodevelopmental aspects. Attention to intellectual disability is mandatory. Any suspicion of a developmental delay in a patient with PUV warrants further investigation and corresponding interventions.

PMID:34158248 | DOI:10.1016/j.jpurol.2021.05.027

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Effect of Adding Bevacizumab to Chemotherapy on Pathologic Response to Preoperative Systemic Therapy for Resectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis

Clin Colorectal Cancer. 2021 May 24:S1533-0028(21)00048-7. doi: 10.1016/j.clcc.2021.05.006. Online ahead of print.

ABSTRACT

BACKGROUND: Liver-limited metastatic colorectal cancer is a potentially curable disease. Pathologic response (pR) to preoperative chemotherapy (CT) for colorectal liver metastases (CLM) is a surrogate endpoint for overall survival (OS). We conducted the first meta-analysis of observational studies to estimate the overall effect of bevacizumab on pR in preoperative systemic therapy for CLM.

METHODS: We systematically searched PubMed, Cochrane Library, CINAHL, Web of Science, Embase, and LILACS for studies published between January 2004 and August 2019 that compared the pR of CT plus bevacizumab to CT alone as preoperative therapy for CLM. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were pathologic major (pMaR) and minor (pMiR) response. Overall effects were expressed by odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model.

RESULTS: Of the 1,452 studies yielded by the search, 9 were eligible, totaling 1,202 patients (516 CT plus bevacizumab and 686 CT alone). The addition of bevacizumab to CT increased the pCR rate without reaching statistical significance (OR: 1.24, 95% CI 0.81 to 1.92, P = .32). However, pMaR was significantly higher (OR: 2.45, 95% CI 1.85 to 3.25, P < .001), and pMiR was significantly lower (OR: 0.41, 95% CI 0.31 to 0.54, P < .001), in the bevacizumab group. The analyses showed a low level of heterogeneity (I2 = 0% to 6%). Publication bias was not found.

CONCLUSIONS: This meta-analysis demonstrates that bevacizumab plus preoperative CT is associated with higher rates of pR in CLM. Antiangiogenics might improve the OS of CLM patients and should be evaluated in randomized clinical trials.

MICROABSTRACT: The benefit of perioperative chemotherapy for colorectal liver metastases (CLM) is uncertain, but pathologic response (pR) to preoperative chemotherapy is a strong prognostic factor. Our meta-analysis of observational studies compared the pR of bevacizumab plus chemotherapy to chemotherapy alone as preoperative systemic therapy in the management of CLM. The addition of bevacizumab was associated with significantly higher rates of pR.

PMID:34158251 | DOI:10.1016/j.clcc.2021.05.006

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Three-dimensional digital measurement of the facet joint in normal and lumbar intervertebral disc herniation aged 13-18 years

Asian J Surg. 2021 Jun 19:S1015-9584(21)00305-5. doi: 10.1016/j.asjsur.2021.05.028. Online ahead of print.

ABSTRACT

BACKGROUND: Lumbar facet joint is an important element of spinal “three-joint complex”. Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults.

OBJECTIVE: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation.

METHODS: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al.

RESULTS: 1. The left and right transverse angle of L5S1 segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L3-L5 segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm2 in male than (18.92 ± 3.71) mm2 in female. 3. In comparison between normal and ALDH group, there was significant difference in L3-4 transverse angle (P < 0.05), L4-5 facet joint height and facet joint thickness (P < 0.05), L5S1 facet joint thickness and transverse angle (P < 0.05).

CONCLUSION: When ALDH occurs in the L5S1 segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.

PMID:34158200 | DOI:10.1016/j.asjsur.2021.05.028

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Single center consecutive series cohort study of partial stomach-partitioning gastrojejunostomy for gastric outlet obstruction

Asian J Surg. 2021 Jun 19:S1015-9584(21)00326-2. doi: 10.1016/j.asjsur.2021.05.047. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Gastric outlet obstruction can have a large impact on quality of life for patients with upper gastrointestinal cancer or benign obstruction. Partial stomach-partitioning gastrojejunostomy has previously shown promising outcomes compared to conventional gastrojejunostomy in terms of reduced delayed gastric emptying. The objective of the current study was to present outcomes of partial stomach-partitioning gastrojejunostomy in a single high-volume center for upper gastrointestinal cancer.

METHODS: A retrospective cohort study including all consecutive patients who underwent partial stomach-partitioning gastrojejunostomy from 2013 to 2020. The primary outcome was oral intake tolerance. A subgroup analysis was performed in all patients with manifest gastric outlet obstruction comparing partial stomach-partitioning gastrojejunostomy to conventional gastrojejunostomy.

RESULTS: Partial stomach-partitioning gastrojejunostomy was performed in 32 patients and laparoscopic technique was used in 19 patients (59%). The procedure improved oral intake tolerance defined by gastric outlet obstruction scoring system by 0.63 points on average (P = 0.041). No postoperative complications related to the procedure were observed. Recurrence of gastric outlet obstruction developed in six patients (19%), four patients (13%) required endoscopic reintervention but no patient required surgical reintervention. A comparison between partial stomach-partitioning gastrojejunostomy and conventional gastrojejunostomy showed no statistically significant differences regarding postoperative nutritional status, length of hospital stay, recurrence or reintervention.

CONCLUSION: The results of the study show that partial stomach-partitioning gastrojejunostomy can be an effective surgical treatment for patients suffering from gastric outlet obstruction and that the procedure can be safely performed with laparoscopic technique.

PMID:34158203 | DOI:10.1016/j.asjsur.2021.05.047

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Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with microsatellite-stable colorectal liver metastases

HPB (Oxford). 2021 Jun 7:S1365-182X(21)00166-0. doi: 10.1016/j.hpb.2021.05.015. Online ahead of print.

ABSTRACT

BACKGROUND: The clinical value of immune checkpoint expression as prognostic biomarker in bevacizumab-pretreated patients with resected microsatellite-stable (MMS) colorectal liver metastases is unclear and was retrospectively investigated in this study.

METHODS: Expression analyses of IDO-1, PD-L1, and CTLA-4 were performed by immunohistochemistry in resected bevacizumab-pretreated colorectal liver metastases. Association of immune checkpoint expression in tumor cells and immune cells with response and clinical outcome was investigated. Expression profiles were compared with those of patients with anti-EGFR-targeted therapy and lung metastases, respectively.

RESULTS: One hundred thirty-six patients with MMS disease were investigated (79 (58.1%) male/57 (41.9%) female, median age 62.9 years (range 31.0-80.4)). High expression of IDO-1 in immune cells was associated with longer OS (not reached versus 44.8 months, HR 0.23 (95% CI 0.09, 0.55), P = 0.001). Low expression of CTLA-4 in tumor cells was associated with better histological response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P = 0.032). Expression profiles differed compared to patients with anti-EGFR-targeted therapy and patients with lung metastases.

CONCLUSION: Immune checkpoint expression was associated with response and survival. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases.

PMID:34158230 | DOI:10.1016/j.hpb.2021.05.015

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Capturing the Healthfulness of the In-store Environments of United Kingdom Supermarket Stores Over 5 Months (January-May 2019)

Am J Prev Med. 2021 Jun 20:S0749-3797(21)00269-5. doi: 10.1016/j.amepre.2021.04.012. Online ahead of print.

ABSTRACT

INTRODUCTION: Numerous environmental factors within supermarkets can influence the healthfulness of food purchases. This research aims to identify the changes in store healthfulness scores and assess the variations by store type and neighborhood deprivation using an adapted Consumer Nutrition Environment tool.

METHODS: Between January and May 2019, a total of 104 supermarkets in London were surveyed on 1-3 occasions. The adapted Consumer Nutrition Environment tool included data on 9 variables (variety, price, quality, promotions, shelf placement, store placement, nutrition information, healthier alternatives, and single fruit sale) for 11 healthy and 5 less healthy food items. An algorithm was used to create a composite score of in-store healthfulness and to assess inter-rater reliability. Longitudinal changes in overall store healthfulness and individual variables were investigated using multivariable hierarchical mixed models. Descriptive statistics were used to describe the differences by store type and neighborhood deprivation in each month. All analyses were conducted between January and July 2020.

RESULTS: The adapted Consumer Nutrition Environment tool showed acceptable inter-rater reliability. Large stores exhibited healthier environments than small stores (p<0.001), with a similar pattern for each of the 9 individual variables. Within large stores, the overall healthfulness score did not change over the study period. Promotions on more healthful items increased in February (p=0.04), and the availability of healthier alternatives for less healthy foods decreased in March (p=0.01). Within small stores, there was a trend toward increasing healthfulness (p<0.001), primarily owing to more promotions on healthy items (p<0.001). There was no difference in overall healthfulness by neighborhood deprivation.

CONCLUSIONS: The adapted Consumer Nutrition Environment tool is sensitive to longitudinal changes in environmental variables that contribute to store healthfulness. A wider application of this tool could be used to map in-store environments to identify targets for interventions to encourage healthier food purchasing.

PMID:34158196 | DOI:10.1016/j.amepre.2021.04.012

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Outcomes following the delayed management of open tibial fractures

Injury. 2021 Jun 2:S0020-1383(21)00492-7. doi: 10.1016/j.injury.2021.05.042. Online ahead of print.

ABSTRACT

AIMS: National guidelines set standards for the definitive management of open fractures within 72 h. This study aims to investigate our outcomes where this timeline was unachievable for most cases due to a split-site orthoplastic service.

PATIENTS & METHODS: 116 consecutive Gustilo-Anderson grade IIIB & IIIC open tibial fractures presenting to our major trauma centre (MTC) between September 2012 and April 2018 were reviewed. The mean follow up was 46 months (17 to 88). 110 (95%) were grade IIIB and 6 (5%) grade IIIC. The most common injury mechanism included road traffic accidents (59%) and falls (28%). Primary outcomes were recorded according to; timing of initial debridement and definitive cover, rates of superficial and deep infection, non-union and amputation. Subgroups were statistically analysed according to time to initial debridement, definitive soft-tissue cover and injury severity score (ISS).

RESULTS: The mean time to initial debridement was 11.3 h (2.9 to 38.9) and definitive soft-tissue cover 9.9 days (0 to 37). We recorded rates of: superficial infection; 42 cases (36%), deep infection; 14 cases (12%) and non-union requiring revision; 19 cases (16%). There were 20 amputations (17%) with 9 (8.6%) performed early and 11 (9.5%) delayed. Subgroup analysis showed higher rates of superficial infection (50%, p = 0.002) and amputation (26.6%, p = 0.01) for those debrided <12 h. A greater presenting ISS related to a delay to definitive cover >7 days (p = 0.05). Primary outcomes trended worse for those covered >7 days but did not reach significance.

CONCLUSION: Major trauma patients are particularly vulnerable to poor outcomes resulting from the delay in definitive management of open fractures. MTC’s need resources and a co-located orthoplastic service to achieve national standards and better outcomes. Current guidelines do not advise for the management of patients where a delay in definitive surgery is anticipated.

PMID:34158158 | DOI:10.1016/j.injury.2021.05.042