Longer Follow-up Time Research Articles

Anemia is associated with increased risk of non-vertebral osteoporotic fractures in elderly men: the MrOS Sweden cohort

SummaryThis study includes 1005 men from the Gothenburg part of the Osteoporotic Fracture in Men Study (MrOS). Included are 66 men with anemia (hemoglobin < 130 g/L). The follow-up time was up to 16 years, and the main results are that anemia is associated with all fractures and non-vertebral osteoporotic fractures.IntroductionAnemia and osteoporotic fractures are conditions that are associated with increased morbidity and mortality. Clinical studies have suggested that anemia can be used as a predictor of future osteoporotic fractures.MethodMen from the Osteoporotic Fractures in Men Study (MrOS) Sweden, Gothenburg, with available hemoglobin (Hb) values (n = 1005, median age 75.3 years (SD 3.2)), were included in the current analyses. Of these, 66 suffered from anemia, defined as Hb < 130 g/L. Median follow-up time for fracture was 10.1 years and the longest follow-up time was 16.1 years.ResultsMen with anemia had, at baseline, experienced more falls and had a higher prevalence of diabetes, cancer, prostate cancer, hypertension, and stroke. Anemia was not statistically significantly associated with bone mineral density (BMD). Men with anemia had higher serum levels of fibroblast growth factor 23 (iFGF23) (p < 0.001) and phosphate (p = 0.001) and lower serum levels of testosterone (p < 0.001) and estradiol (p < 0.001). Moreover, men with anemia had an increased risk of any fracture (hazard ratio (HR) 1.97, 95% CI 1.28–3.02) and non-vertebral osteoporotic fracture (HR 2.15, 95% CI 1.18–3.93), after adjustment for age and total hip BMD, in 10 years. The risk for any fracture was increased in 10 and 16 years independently of falls, comorbidities, inflammation, and sex hormones. The age-adjusted risk of hip fracture was increased in men with anemia (HR 2.32, 95% CI 1.06–5.12), in 10 years, although this was no longer statistically significant after further adjustment for total hip BMD.ConclusionsAnemia is associated with an increased risk for any fracture and non-vertebral osteoporotic fracture in elderly men with a long follow-up time. The cause is probably multifactorial and our results support that anemia can be used as a predictor for future fracture.

P570: REAL-WORLD EFFICACY OUTCOMES OF VENETOCLAX PLUS AZACITIDINE VS INTENSIVE CHEMOTHERAPY FOR INDUCTION THERAPY IN ADULT PATIENTS WITH ACUTE MYELOID LEUKEMIA

Background: Intensive chemotherapy (IC) is commonly used to achieve remission in patients with newly diagnosed acute myeloid leukemia (AML), although the relapse rate remains high. The combination of venetoclax, a BCL2 inhibitor, plus intravenous or subcutaneous azacitidine (ie, VEN-AZA), is FDA- and EMA-approved for the treatment of patients with newly diagnosed AML aged ≥ 75 years or with comorbidities that preclude the use of IC. Because of the challenging induction and maintenance decisions for some patients, it is important to understand the real-world patterns of use and outcomes of VEN-AZA vs IC. Aims: To compare US real-world outcomes for the use of VEN-AZA vs IC, particularly in older populations. Methods: This retrospective analysis was performed on a cohort of patients from the US-based Flatiron Health electronic health record-derived de-identified database, who had newly diagnosed AML and received induction therapy with VEN-AZA or IC between 21 Nov 2018 and 01 Jun 2021. Using an intention-to-treat analysis (including patients with less than 2 months of follow-up), patient groups were propensity score-matched in a 1:1 ratio using nearest neighbor matching with calipers set to 0.01 to reduce bias. Matched-patient assessments included morphological complete remission, overall survival (OS; defined as from first day of therapy to death), and relapse-free survival (RFS; from first day of therapy to relapse or death). Univariate analyses were used to investigate possible treatment-associated OS and RFS benefit in patient subgroups, including those with high-risk mutations. Results: Of 7484 patients in the Flatiron database with newly diagnosed AML, 1188 met the selection criteria and 436 were propensity score-matched resulting in 218 per treatment group. In the matched VEN-AZA vs IC cohorts, patients had a mean age of 69.9 vs 69.0 y and Charlson Comorbidity Index of 0.5 vs 0.7, respectively; 39% vs 38% were female. The rates of patients with complete remission (CR) and those with stem cell transplant (SCT) were significantly lower with VEN-AZA vs IC at 46% vs 62% (P=0.001) and 16% vs 31% (P<0.001), respectively. Fewer VEN-AZA– vs IC-treated patients received an early posttreatment bone marrow biopsy, with respective rates of 31% vs 69% (1 mo) and 57% vs 86% (2 mo). Median OS for VEN-AZA vs IC in the matched population was 13.0 vs 17.2 mo (P=0.263), respectively; it was 11.0 vs 15.6 mo (P=0.410) with censoring for SCT. Median RFS was numerically shorter for VEN-AZA than for IC (9.5 vs 11.0 mo; P=0.689); when including censoring for SCT, RFS was longer for VEN-AZA (7.5 vs 5.7 mo; P=0.027). Among subgroups, including those with high-risk mutations, no significant factor was found to be associated with OS in the matched patients (Figure). The frequency of known patients with high-risk mutations in RUNX1, ASXL1, and TP53 was similar for both treatment groups. Similar subgroup results were observed for RFS. Image:Summary/Conclusion: Rates of CR and SCT were significantly higher with IC. OS was nominally longer with IC vs VEN-AZA, with and without censoring for SCT; differences were not statistically significant. None of the subgroups tested, including patients with high-risk mutations, showed a significant OS association. Longer follow-up time may contribute to better characterized outcomes achieved with IC vs VEN-AZA in routine clinical practice. These data support more investigation on strategies to improve survival outcomes, including the impact of maintenance therapy.

The efficacy and tolerability of antibiotics in scrub typhus: an updated network meta-analysis of randomized controlled trials

ObjectivesInadequate treatment of scrub typhus results in severe complications such as septic shock and is also associated with a high median mortality rate of 6%. However, there has been no conclusive evidence about the superiority of different antibiotics in managing scrub typhus in terms of efficacy and tolerability. MethodsWe conducted a network meta-analysis (NMA) using the frequentist method. The included participants were pediatric and adult patients infected with scrub typhus. The primary outcome was the cure rate in the patients included. The subgroup analysis was done according to pediatric or adult patients. ResultsOverall, 14 randomized controlled trials (RCTs) with 1264 participants were included in this study. The NMA revealed that all the investigated antibiotics were associated with cure rates similar to those of doxycycline. The chloramphenicol and minocycline were ranked to be associated with the highest cure rate in the pediatric subgroup and adult subgroup, respectively. Second-generation quinolones, including ofloxacin, ciprofloxacin, and chloramphenicol, were associated with significantly lower adverse event rates than doxycycline. ConclusionThe current updated NMA provides evidence for the efficacy of chloramphenicol and minocycline in scrub typhus management. However, future large-scale RCTs with longer follow-up times are warranted.

Real-world outcomes of biosimilar bevacizumab-awwb versus reference bevacizumab in patients with metastatic colorectal cancer.

3552 Background: Bevacizumab-awwb was the first biosimilar approved by the U.S. Food and Drug Administration (FDA) for treatment of cancer and became available for use in July 2019. Clinical comparative efficacy and safety of bevacizumab-awwb to bevacizumab was established in a single study of adult patients with advanced non-squamous non-small cell lung cancer. Approval based on extrapolation was granted by the FDA for all other indications, including metastatic colorectal cancer (mCRC). The objective of this study was to evaluate the real-world effectiveness and safety outcomes of patients with mCRC initiated on bevacizumab-awwb versus bevacizumab in an integrated healthcare delivery system. Methods: This was an observational cohort study of patients with mCRC in Kaiser Permanente California, Colorado, and Mid-Atlantic States who were initiated on bevacizumab-awwb between July 2019 and March 2020 or reference bevacizumab between July 2015 and June 2018. Patients with history of bevacizumab use in the 6 months prior to the index treatment date were excluded. Patients were followed until 12 months after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a non-inferiority test with lower margin of 10% and Cox proportional-hazards modeling. Secondary outcomes included count of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events. Results: A total of 1,445 patients initiated on either bevacizumab-awwb (n=239) or bevacizumab (n=1,206) were included in the analysis. The mean overall age was 60 ± 13 years and 54% of patients were male. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab, respectively ( p&lt;0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p=0.93). There were no statistically significant differences in secondary outcomes between the 2 study groups (Table). Conclusions: Bevacizumab-awwb is a safe and effective option when compared to the reference bevacizumab in the treatment of mCRC. Future studies should evaluate outcomes after longer follow-up time and in different cancer types. [Table: see text]

COVID-19 AND CARDIOVASCULAR SYSTEM: NOT ONLY HEART BUT ALSO VASCULAR. THE EFFECTS OF THE INFECTION ON ARTERIAL STIFFNESS

Objective: SARS-CoV-2 determines a framework of multi-organ dysfunction that can involve the cardiovascular system creating damages of different nature. Among these, endothelial damage could play a key role in increasing arterial stiffness and thus the cardiovascular risk of infected patients. The aim of this study is to evaluate the Pulse Wave Velocity (PWV) of a population of patients after recovery from infection and to compare them with those of a group affected by arterial hypertension. Design and method: This prospective observational monocentric study involved 143 patients with previous diagnosis of Covid-19 who undergone PWV measurement during the follow-up at a median time of 3.8 months after the infection. These patients were compared to a population of 143 patients with hypertension matched by age, sex, Systolic Blood Pressure values and Body Mass Index. Results: PWV values were higher in Covid-19 group comparing to hypertension group (10.5 ± 3.0 m/s VS 8.9 ± 2.5 m/s). Furthermore, there is a correlation between higher PWV values and lower values of SpO2% at time of admission at the Emergency Department. (R = -0.302; p &lt; 0.001). Conclusions: SARS-CoV-2 infection seems related to increased PWV values. Moreover, higher arterial stiffness seems correlated to a worse oxygen saturation in Emergency Department. More studies with longer follow-up time are necessary to establish whether the vascular damage is reversible and whether it correlates with an increase of long-term cardiovascular risk.

Transcranial direct current stimulation in the management of phantom limb pain: a systematic review of randomized controlled trials.

Phantom limb pain (PLP) after amputation is a frequent entity that conditions the life of those who suffer it. Current treatment methods are not sufficiently effective for PLP management. We aim to analyze the clinical application of transcranial direct current (tDCS) in people with amputation suffering from PLP. The following databases were consulted in September 2021: MEDLINE, EMBASE, The Web of Science, PEDro, SCOPUS and SciELO. Randomized controlled trials investigating the use of tDCS in people with amputation undergoing PLP were selected. Demographic data, type and cause of amputation, time since amputation, stimulation parameters, and outcomes were extracted. Six articles were included in this review (seven studies were considered because one study performed two individual protocols). All included studies evaluated PLP; six evaluated the phantom limb sensations (PLS) and two evaluated the psychiatric disorders. In all included studies the intensity and frequency of PLP was reduced, in three PLS were reduced, and in none study psychiatric symptoms were modified. Anodic tDCS over the contralateral M1 to the affected limb, with an intensity of 1-2 mA, for 15-20 minutes seems to significantly reduce PLP in people with amputation. Single-session treatment could modify PLP intensity for hours, and multi-session treatment could modify PLP for months. Limited evidence suggests that PLS and psychiatric disorders should be treated with different PLP electrode placements. Further studies with larger sample size and longer follow-up times are needed to establish the priority of tDCS application in the PLP management.

Assessing surrogacy using restricted mean survival time ratio for overall survival in liver cancer immunotherapy studies.

e16222 Background: Recently, immunotherapy has played a crucial role in treating liver cancer, one of the major cancers that contributes to global cancer burden. Overall survival (OS) is widely applied in cancer trials to evaluate the treatment effects of new therapies. However, it requires more patients and longer follow-up time comparing with progression-free survival (PFS). In addition, while assessing the treatment effects of cancer immunotherapy, proportional hazard (PH) assumption is often violated due to issues such as delayed treatment effects. Restricted Mean Survival Time (RMST) ratio is increasingly used for treatment effect evaluation when the PH assumption is violated. Such change prompts an important question whether the surrogacy value of PFS will be affected when RMST ratio is used to characterize treatment effect. The aim of this study is to examine the feasibility of using PFS as a surrogate endpoint for OS when the treatment effect is measured using hazard ratio (HR) versus RMST ratio. Methods: The surrogacy of PFS on OS was evaluated through examining the association between PFS and OS using HR and RMST ratio. Seven immunotherapy studies published between 2000 and 2021 were included (Table). Information of examined studies such as treatment arms information, OS and PFS were collected. RMST ratio for PFS and OS were calculated based on the Kaplan-Meier plots extracted from each article using WebPlotDigitizer 4.4. The weighted least square regression lines and R^2 between OS and PFS for HR and RMST ratio were calculated. Results: Among 7 immunotherapy studies, 4 gave placebos to the control arms as treatments. 2 provided Sorafenib and 1 assigned the same drug as treatment arm but with different schedule. All 7 studies had OS and PFS as the endpoints. 2 studies violated the PH assumptions. Based on the data extracted from examined articles, a moderate correlation (0.52) between PFS and OS was observed for HR while low correlation (0.10) was observed for RMST ratio. Conclusions: The R^2 values differ greatly depending on whether HR or RMST ratio was used for assessing surrogacy. Our finding may have important implications for the design of future immunotherapy liver cancer trials. For future work, increasing the number of included studies for a more comprehensive analysis is needed. Moreover, trial-level surrogacy analysis should be conducted to complement the study-level investigation.[Table: see text]

The effect of COVID-19 on poor treatment control among ambulatory Hypertensive and/or Diabetic patients in Northwest Ethiopia

Diabetes and hypertension have emerged as important clinical and public health problems in Ethiopia. The need to have long-term sustainable healthcare services for patients with diabetes and hypertension is essential to enhance good treatment control among those patients and subsequently delay or prevent complications. A collective shift towards acute care for COVID-19 patients combined with different measures to contain the pandemic had disrupted ambulatory care. Hence, it is expected to have a significant impact on treatment control of hypertensive and diabetic patients. However, there is limited evidence on the effect of the pandemic on treatment control and its determinants. Therefore, this study aimed to assess the effect of COVID-19 pandemic on treatment control of ambulatory Hypertensive and Diabetic patients and identify the factors for poor treatment control in North West Ethiopia. A retrospective chart review and cross-sectional survey design were conducted between December 2020 and February 2021. Using a stratified systematic random sampling technique, 836 diabetic and/or hypertensive patients were included in the study. Web-based data collection was done using Kobo collect. The changes in the proportion of poor treatment control among ambulatory Hypertensive and/or Diabetic patients during the COVID-19 pandemic period were assessed. A multivariable binary logistic regression mixed model was fitted to identify the determinants of poor treatment control. The odds ratios were reported in both crude and adjusted form, together with their 95% confidence intervals and p-values. Poor treatment control increased significantly from 24.81% (21.95, 27.92) prior to the COVID-19 pandemic to 30.33% (27.01, 33.88), 35.66% (32.26, 39.20), 36.69% (33.40, 40.12), and 34.18% (3102, 37.49) in the first, second, third, and fourth months following the date of the first COVID-19 case detection in Ethiopia, respectively. Marital status (AOR = 0.56, 95%CI; 0.41, 0.74), regimen of medication administration (AOR = 1.30, 95%CI; 1.02, 166), daily (AOR = 0.12, 95%CI; 0.08, 0.20), twice (AOR = 0.42, 95%CI; 0.30. 0.59), and three times (AOR = 0.31, 95%CI; 0.21, 0.47) frequency of medication, number medications taken per day (AOR = 0.79, 95%CI;0.73, 0.87), patients habits like hazardous alcohol use (AOR = 1.29, 95%CI; 1.02, 1.65) and sedentary lifestyle (AOR = 1.72,95%CI;1.46, 2.02), missed appointment during the COVID-19 pandemic (AOR = 2.09, 95%CI; 1.79, 2.45), and presence of disease related complication (AOR = 1.11, 95%CI; 0.93, 1.34) were significantly associated with poor treatment control among Diabetic and/or hypertensive patients during the COVID-19 pandemic. The COVID-19 pandemic had a substantial impact on ambulatory Diabetic and/or Hypertensive patients' treatment control. Being married, as well as the frequency and types of medicines taken per day were all found to be negatively associated with poor treatment control. During the COVID -19 pandemic, patients' habits such as hazardous alcohol use and sedentary lifestyle, longer follow-up time, having disease-related complication (s), patients taking injectable medication, number of medications per day, and missed appointments were positively associated with poor treatment control in ambulatory diabetic and hypertensive patients. Therefore, it is better to consider the risk factors of poor treatment control while designing and implementing policies and strategies for chronic disease control.

The effect of implantable cardioverter defibrillator in patients with cardiac resynchronizational therapy and diabetes mellitus

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): (NKFIA; NVKP_16-1-2016-0017 National Heart Program). Background Heart failure (HF) and diabetes mellitus (DM) are common causes of death on their own, but the coexistance of these two diseases are especially fatal. 1 In DM, sudden cardiac death (SCD) is more common than in non-DM patients, however in many cases, implantable cardioverter defibrillator (ICD) could not prevent SCD. 2 Purpose Our aim is to decide which device warrant higher life expectancy, cardiac resynchronizational therapy with or without defibrillator. Methods We examined retrospectively 2525 CRT implanted patients, with a mean follow-up time of 4.6 years. Implantaions were based on the current guidelines. The primary endpoint was all-cause mortality, while our composite end-point were all-cause mortality and heart failure hospitalization. Results In our population, 928 people (36%) had diabetes. We did not find statistical differences between age (68 vs. 68 years; p&amp;lt;0.099), gender (26% women, 23% women; p&amp;lt;0.08) LVEF (28% vs. 29% p&amp;lt;0.1425), incidence of atrial fibrillation (37% vs. 38%; p&amp;lt;0.76), implantation of an ICD (53% vs. 54%; p&amp;lt;0.847), NT-proBNP median levels (2939 pg/ml vs. 2778 pg/ml; p&amp;lt;0.35), and NYHA I (0,5% vs. 0,5%; p&amp;lt;0.898), and NYHA IV stadium (11% vs. 11%; p&amp;lt;0,82). However DM patients had higher BMI (28 kg/m2 vs. 26 kg/m2; p&amp;lt;0.001), lower eGFR levels (57 ml/min/1,73m2 vs. 60 ml/min/1,73m2; p&amp;lt;0.011) higher prevalence of hypertonia (82% vs. 66%; p&amp;lt;0.001), NYHA III stadium (39% vs. 33%; p&amp;lt;0,0008), ischemic etiology (56% vs. 44%; p&amp;lt;0.001), previous acute myocardial infartion (42,9% vs. 36%; p&amp;lt;0.001), a percutan coronaria intervention (35% vs. 25%; p&amp;lt;0.001) compared to non-DM patients. Those patients with DM showed a 25% higher risk of all-cause mortality (HR 1.25; 95% CI 1.12-1.40; p‹0.01) then non-DM patientes, also observable after adjusting for relevant clinical covariates such as age, gender, atrial fibrillation and the addition of an ICD (HR 1.17; 95% CI 1.06-1.31; p‹0.01). Conclusions Adding an ICD for CRT patients with diabetes reduces the risk of all-cause mortality significantly by 32% (HR 0,68; CI 0,56-0,82; p‹0.001) during the first six years but diminished on longer follow-up time (HR 0,95; CI 0,80-1,12; p=0,54).

Neural activity of the auditory cortex predicts speech recognition of patients with asymmetric hearing loss after cochlear implantation

Patients with asymmetric hearing loss show an asymmetry of glucose metabolism of the primary auditory cortex (PAC). We investigated whether this asymmetry could serve as an objective predictor for speech recognition with CI. Nine patients underwent 18FDG PET prior to CI surgery. Average normalized 18FDG uptake of 25% of voxels with highest uptake was calculated for the PAC employing a probabilistic atlas and cerebellar cortex as reference. Differences in glucose metabolism of the PAC were assessed by an asymmetry index (AI-PAC). We tested the correlation between outcome of CI surgery (6 months post implantation), AI-PAC and clinical predictors. Pre-operative AI-PAC showed a positive correlation with speech recognition with CI (significant for sentences and numbers; trend for monosyllabic words). With a pre-operative AI-PAC ≥ 4.2%, patients reached good CI outcome in sentence recognition of 59–90% and number recognition of 90–100% and less favorable CI outcome in monosyllabic word recognition of 25–45%. Age at symptom onset was significantly associated with all measures of speech recognition, while deafness duration was only associated with sentence recognition. AI-PAC allows for a reliable and quantitative pre-operative prediction of early improvement in speech recognition after CI. 18FDG PET may be a valuable addition to the objective pre-operative assessment of CI candidates. Further studies in larger cohorts and with longer follow-up times are needed.

Comparison of Ambulatory Health Care Costs and Use Associated With Roux-en-Y Gastric Bypass vs Sleeve Gastrectomy

Studies comparing contemporary bariatric surgical types could facilitate procedure selection for patients interested in reducing their frequency of health care visits and reliance on prescription drugs. To compare the association of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) with ambulatory health care costs and use for as long as 4 years after surgery. This comparative effectiveness study, which included patients undergoing bariatric surgery who were aged 18 to 64 years with at least 24 months of enrollment data before surgery and 12 months of enrollment data after surgery, used a retrospective interrupted time series with a comparison group. Data represent insurance claims dated January 2006 to June 2017, with analyses completed in September 2021. Data were collected from US commercial and Medicare Advantage claims database. Cohorts were matched on characteristics including baseline body mass index category, diabetes status, baseline ambulatory care costs, region of the United States, and year of surgery. SG or RYGB, based on procedure codes. Annual ambulatory health care costs, and subtypes of cost and use including prescriptions, office visits, laboratory encounters, and radiology. Matched cohorts included 3049 patients who underwent SG and 3251 patients who underwent RYGB, with a mean (SD) age of 45.2 (10.0) years; 4820 (77%) were women. Full follow-up was 37% for SG (514 patients) and 38% for RYGB (643 patients) among those eligible for 4-year follow-up. There were no significant differences between SG and RYGB in total ambulatory costs, office visit costs, or radiology costs in all follow-up years. Patients who underwent SG had significantly higher prescription costs than those who underwent RYGB bypass in year 4 ($852.8 per patient per year; 95% CI: $395.6-$1310.0 per patient per year) with more cardiometabolic medication fills in each year (eg, year 4: 42.5%; 95% CI, 13.7%-71.2%). In contrast, early after surgery, patients who underwent SG had relatively fewer specialist visits (eg, year 1: -7.2%; 95% CI, -14.3% to -0.2%) and lower laboratory costs (eg, year 1: -$118.9 per patient per year; 95% CI, -$220.2 to -$17.5 per patient per year). Despite clinical studies showing greater weight loss and comorbidity improvement with RYGB vs SG, this study found no difference in total ambulatory costs for as long as 4 years after SG and RYGB. These findings may reflect the trade-off between greater improvements in cardiometabolic health and additional surgery-related care among patients undergoing RYGB. Studies with longer follow-up time could determine whether greater sustained weight loss from RYGB eventually results in lower costs compared with SG.

A meta-analysis of visual outcomes and optical quality after small incision lenticule extraction versus implantable collamer lens for myopia.

To evaluate possible differences in visual outcome and optical quality when small incision lenticule extraction (SMILE) versus implantable collamer lens (ICL) is used to correct myopia. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched up to August 2021 to identify relevant studies. The PRISMA guidelines were followed. Primary outcomes were postoperative efficacy, safety, and predictability at the end of follow-up. Secondary outcomes were changes in modulation transfer function cutoff frequency (MTF cut-off), objective scatter index (OSI) values, total higher-order aberrations (HOAs), spherical aberrations, and coma aberrations. Seven studies with a total of 1296 eyes (SMILE: 731 eyes; TECXL: 565 eyes) were included. The ICL group had a better MTF cut-off (P = 0.007) and less change in the proportion of HOAs (P < 0.001), spherical aberrations (P = 0.009), and coma (P = 0.006) than the SMILE group. For the other outcomes, there were no statistically significant differences. SMILE and ICL implantation are comparable in efficacy, safety, and predictability for correcting myopia. Larger studies with longer follow-up times are warranted to provide a better understanding of the benefits of SMILE and ICL implantation.

A Narrative Review about Autism Spectrum Disorders and Exclusion of Gluten and Casein from the Diet.

Objective: Autism spectrum disorders (ASDs) appear in the early stages of neurodevelopment, and they remain constant throughout life. Currently, due to limitations in ASDs treatment, alternative approaches, such as nutritional interventions, have frequently been implemented. The aim of this narrative review is to gather the most relevant and updated studies about dietary interventions related to ASDs etiopathogenesis. Results: Our literature search focused on the gluten- and casein-free (GFCF) diet. The literature found shows the inexistence of enough scientific evidence to support a general recommendation of dietary intervention in children with ASD. Protocols and procedures for assessing risk and safety are also needed. Future lines: Prospective and controlled research studies with larger sample sizes and longer follow-up times are scarce and needed. In addition, studies considering an assessment of intestinal permeability, bacterial population, enzymatic, and inflammatory gastrointestinal activity are interesting to identify possible responders. Besides brain imaging techniques, genetic tests can also contribute as markers to evaluate the comorbidity of gastrointestinal symptoms.

Higher Incidence of Diabetes in Cancer Patients Compared to Cancer-Free Population Controls: A Systematic Review and Meta-Analysis.

Simple SummaryDiabetes increases the risk of certain types of cancer. However, the literature regarding the incidence of diabetes after cancer diagnosis is inconsistent. We aimed to assess whether there was a higher incidence of diabetes among cancer patients by performing a systematic review and meta-analysis of results from cohort studies. To the best of our knowledge, this review conducted the largest and most up-to-date meta-analysis to compare the incidence of diabetes between cancer patients and the cancer-free population. Our results suggest that new-onset diabetes is positively associated with cancer.Background: Diabetes increases the risk of certain types of cancer. However, the literature regarding the incidence of diabetes after cancer diagnosis is inconsistent. We aimed to assess whether there was a higher incidence of diabetes among cancer patients by performing a systematic review and meta-analysis of results from cohort studies. Methods: A systematic electronic literature search was carried out from cohort studies regarding the incidence of diabetes in cancer patients, using the databases PubMed (MEDLINE), Embase, Web of Science, and the Cochrane Library. Random-effects meta-analyses were conducted to pool the estimates. Results: A total of 34 articles involving 360,971 cancer patients and 1,819,451 cancer-free controls were included in the meta-analysis. An increased pooled relative risk (RR) of 1.42 (95% confidence interval (CI): 1.30–1.54, I2 = 95, τ2 = 0.0551, p < 0.01) for diabetes in cancer patients was found compared with the cancer-free population. The highest relative risk was observed in the first year after cancer diagnosis (RR = 2.06; 95% CI 1.63–2.60). Conclusions: New-onset diabetes is positively associated with cancer, but this association varies according to cancer type. More prospective studies with large sample sizes and longer follow-up times are advocated to further examine the association and the underlying mechanisms.

Assessing The Clinical Benefits Of Iv Iron-only In Heart Failure Patients: A Meta-analysis

<h3>Introduction</h3> The cost of heart failure (HF) continues to be a huge burden on the healthcare system, with recurrent hospitalizations and mortality being major contributors.¹ Iron deficiency (ID) is a commonly undertreated comorbidity in HF patients, despite research showing its association with increased mortality and hospitalization rates.² <h3>Objective</h3> We aim to perform a meta-analysis of randomized controlled trials (RCT) assessing the clinical benefits of treating iron deficiency in heart failure patients. <h3>Methods</h3> We searched Pubmed, Cochrane, EMBASE and NIH databases from 2005-2020. The result was limited to RCT's comparing intravenous (IV) iron-only to placebo, in HF patients with ID. We identified 7 RCT's for inclusion.^3-9 Intervention used in selected trials was IV iron (iron sucrose or ferric carboxymaltose). The primary outcome was the incidence of HF hospitalization, and the secondary outcome was all-cause mortality at maximum follow-up time. A random-effects model was used. The bias of included studies was assessed using the Cochrane bias assessment for RCT's. The analysis was performed using Cochrane Revman version 5.3. <h3>Results</h3> Seven studies were included, with 2,164 participants (1,167 IV Iron group, 997 Placebo group). There were no significant differences in the baseline characteristics of the groups. Follow-up time ranged from 12-52 weeks. Compared to placebo, IV iron significantly reduces the odds of HF hospitalization events in HF patients with ID (OR: 0.54; 95% CI: 0.32 to 0.91; p=0.02) [Figure 1]. Rates of all-cause mortality in the IV iron group were no different than in the placebo group (OR: 0.92; 95% CI: 0.68 to 1.24; p=0.60) [Figure 2]. <h3>Conclusion</h3> Treatment with IV iron compared to placebo significantly reduces the incidence of HF hospitalization in HF patients with ID. Conversely, there was no mortality benefit with using IV iron over placebo in HF patients with ID. Our study represents the largest number of meta-analyzed patients and expands on the recent meta-analysis by Osman et al.¹⁰ by including all types of HF (HFpEF and HFrEF) patients. Further study of the use of IV iron with longer follow-up time is needed to further explore the clinical benefits of IV iron in HF patients with ID.

Intraocular lens implantation in the absence of capsular support.

In the absence of capsular support, it is not always possible to safely place an intraocular lens (IOL) in the capsular bag at the time of surgery. Several techniques have thus been developed to enable safe placement of a secondary IOL outside the capsular bag. These techniques include placement of anterior chamber IOLs, iris-fixated IOLs (sutured, iris-claw), and scleral-fixated IOLs (sutured, sutureless). Secondary IOL placement can take place at the time of the initial surgery or in a second surgery. Each technique has its own unique advantages, as well as its potential complications. At this time, comparison studies have found no secondary IOL technique to be superior in terms of visual acuity or rate of complications. Additional comparison studies with longer follow-up times are needed to confirm these findings. The decision on which secondary IOL technique to perform depends on numerous factors including surgeon experience and comfort, as well as patient comorbidities.

Stool Management Followed by Surgical Debridement and Surgical Closure Combined With Negative Pressure Wound Therapy in the Treatment of Posterior Trunk Pressure Injury: A Retrospective Descriptive Study

BACKGROUND: Pressure injuries are a burden to patients and the health care system, and negative pressure wound therapy (NPWT) is a widely used treatment. PURPOSE: This study sought to assess the effect of stool management followed by surgical debridement and surgical closure combined with NPWT in the treatment of posterior trunk pressure injuries. METHODS: A retrospective descriptive study was conducted in patients with stage 3 or 4 posterior trunk pressure injuries by reviewing electronic health records. The collected variables included sex, age, height, weight, initial underlying disease leading to being bedridden, stage and anatomical location of pressure injury, stool frequency, pathogens, number of NPWT applications, complications related to surgical closure, outcome, and treatment time. Fasting and enema were used to reduce the frequency of defecation, followed by surgical debridement and surgical closure combined with NPWT. RESULTS: Among the 63 eligible patients, 35 were male and 28 were female (average age, 72.3 ± 11.3 years). The patients’ weight before fasting and after fasting showed no significant difference (62.6 ± 11.2 kg vs 61.6 ± 10.2 kg; 95% confidence interval, -2.78–4.76; P = .60). Stage 3 and stage 4 accounted for 33 (52.4%) and 30 (47.6%) pressure injuries, respectively. There were 36 (57.1%) pressure injuries located on the sacrum, and the remaining 27 (42.9%) were located in the ischia. Underlying causes for being bedridden were cardiopulmonary insufficiency (n = 23; 36.5%), severe brain damage and cerebrovascular accident (n = 19; 30.2%), spinal cord injury (n = 12; 19.0%), and others (14.3%). The wound closure rate was 96.8% (n = 61), with a mean hospital stay of 22.3 days. These patients underwent 1 to 3 cycles of NPWT before surgical wound closure. Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa were the most common pathogens. The complications related to surgical closure (defined as complications that occurred from surgical closure until 30 days later) occurred in 7 patients (11.1%); 3 patients (4.8%) experienced a pressure injury recurrence. CONCLUSION: The treatment approach reported here was effective in these patients with posterior trunk pressure injuries. A satisfactory cure rate, manageable complications, and rare recurrence were achieved. Parenteral nutrition after fasting maintained patients’ weight without significant loss. Prospective randomized controlled trials involving larger samples and longer follow-up times are needed.

Single vocal cord irradiation for early-stage glottic cancer: Excellent local control and favorable toxicity profile

ObjectiveTo validate the earlier reported promising oncologic outcomes and favorable toxicity profile following single vocal cord irradiation (SVCI) in an expanded cohort of patients with early-stage glottic cancer treated at our institute with longer follow-up time. Materials and methodsBetween February 2011 and January 2020, 111 consecutive patients with early-stage glottic cancer were treated with SVCI to the whole involved vocal cord (58.08 Gy, given in 16 fractions of 3.63 Gy). Setup verification was done using cone-beam CT, prior to each fraction. The endpoints were local control (LC), overall survival (OS), grade ≥ 3 toxicity and voice quality assessment using voice-handicap index (VHI) questionnaires. ResultsMedian follow-up was 41 months (range; 8–84). Two patients developed in-field local failure (LF). The 3- and 5-year LC rates were 99.1% and 97.1%, respectively. As both patients with LF were successfully salvaged with total laryngectomy, the 5-year ultimate LC-rates was 99%. The 5-years OS was 80.6%. All patients finished treatment without any interruption. No patients developed acute grade ≥ 3 toxicity. Late grade 3 toxicity was reported in 7 patients (6.5%) out of 108 patients evaluable for late toxicity; 2 because of severe hoarseness and 5 because of laryngeal radionecrosis (4.5%). The 5-years laryngectomy-free survival was 98.1%. The VHI-scores improved over time, only 22% of patients had VHI > 30 at 3-years post-radiotherapy, compared to 38% at baseline. ConclusionsLocal control rate and laryngectomy-free survival of SVCI are excellent with favorable toxicity profile and good VHI-score. These results validate our early results.

Nodular fasciitis of the breast: the report of three cases

BackgroundNodular Fasciitis is a benign fibroblastic proliferation in soft tissues, which mostly occurs in the upper extremities, trunk, head and neck region. It is rarely reported to occur in the breast.Case presentationHerein, we present sonograms of nodular fasciitis in the breast at different durations in three cases. In Case 1, we provided the longest follow-up time in all literatures. In Case 2 and Case 3, we provided the automated breast ultrasound finding of breast nodular fasciitis for the first time.ConclusionNodular Fasciitis shows clinical features and ultrasonography findings are similar to those of breast cancer. For superficially located breast lesions with a single and rapid growth, nodular fasciitis may be considered in the differential diagnosis of benign entities resembling malignant tumors on breast imaging.

Comparison of Moderna versus Pfizer-BioNTech COVID-19 vaccine outcomes: A target trial emulation study in the U.S. Veterans Affairs healthcare system.

SummaryBackgroundmRNA COVID-19 vaccines manufactured by Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) have been shown to be efficacious but have not been compared in head-to-head clinical trials.MethodsWe designed this observational study to emulate a target trial of COVID-19 vaccination by BNT162b2 versus mRNA-1273 among persons who underwent vaccination in the national U.S. Veterans Affairs (VA) healthcare system from 11/12/2020 to 25/03/2021 using combined VA and Medicare electronic health records. We identified the best matching mRNA-1273 recipient(s) for each BNT162b2 recipient, using exact/coarsened-exact matching (calendar week, VA integrated service network, age buckets and Charlson comorbidity index buckets) followed by propensity score matching. Vaccine recipients were followed from the date of first vaccine dose until 25/08/2021 for the development of SARS-CoV-2 infection, SARS-CoV-2-related hospitalization or SARS-CoV-2-related death.FindingsEach group included 902,235 well-matched vaccine recipients, followed for a mean of 192 days, during which 16,890 SARS-CoV-2 infections, 3591 SARS-CoV-2-related hospitalizations and 381 SARS-CoV-2-related deaths were documented. Compared to BNT162b2, mRNA-1273 recipients had significantly lower risk of SARS-CoV-2 infection (adjusted hazard ratio [aHR] 0.736, 95% CI 0.696–0.779) and SARS-CoV-2-related hospitalization (aHR 0.633, 95% CI 0.562–0.713), which persisted across all age groups, comorbidity burden categories and black/white race. The differences between mRNA-1273 and BNT162b2 in risk of infection or hospitalization were progressively greater when the follow-up period was longer, i.e. extending to March 31, June 30 or August 25, 2021. These differences were more pronounced when we analyzed separately the outcomes that occurred during the follow-up period from July 1 to August 25, 2021 when the Delta variant became predominant in the U.S. (aHR for infection 0.584, 95% CI 0.533–0.639 and aHR for hospitalization 0.387, 95% 0.311–0.482). SARS-CoV-2-related deaths were less common in mRNA-1273 versus BNT162b2 recipients (168 versus 213) but this difference was not statistically significant (aHR 0.808, 95% CI 0.592–1.103).InterpretationIn conclusion, although absolute rates of infection, hospitalization and death in both vaccine groups were low regardless of the vaccine received, our data suggests that compared to BNT162b2, vaccination with mRNA-1273 resulted in significantly lower rates of SARS-CoV-2-infection and SARS-CoV-2-related hospitalization. These differences were greater with longer follow-up time since vaccination and even more pronounced in the Delta variant era.FundingU.S. Department of Veterans Affairs, grant numbers COVID19–8900–11 and C19 21–278.