Aromatase inhibitors versus tamoxifen as adjuvant hormonal therapy for oestrogen sensitive early breast cancer in post-menopausal women: Meta-analyses of monotherapy,sequenced therapy and extended therapy

Adjuvant tamoxifen reduces relapses and prolongs survival in patients with oestrogen sensitive breast cancer. Development of resistance is however common. Tamoxifen can be given for a maximum of five years; although the risk of recurrences remains high after this period. This review examines nine randomised controlled trials including 28 632 women, which studied aromatase inhibitors (AIs) as an alternative to tamoxifen in three treatment settings: monotherapy (instead of tamoxifen), sequenced therapy (tamoxifen is switched to an AI) and extended therapy (following adjuvant tamoxifen). Disease free survival was significantly improved for monotherapy (HR 0.89, [95% CI 0.83–0.96] p = 0.002) and sequenced therapy (HR 0.72, [0.63–0.83] p < 0.00001). There was no difference in overall survival for monotherapy (HR 0.94, [0.82–1.08] p = 0.39) or extended therapy (HR 0.86 [0.79–1.16] p = 0.67). Importantly, overall survival was prolonged for patients who switched from tamoxifen to AI therapy (HR 0.78 95%CI 0.68–0.91, p = 0.001).     

Risk factors associated with venous thromboembolism in 49,028 mastectomy patients

Venous thromboembolism (VTE) is a potentially preventable disease that carries significant morbidity and mortality. Although malignancy is associated with increased risk for VTE, it varies according to cancer type. Despite the fact that breast cancer is the most common form of cancer in women, the incidence and risk factors associated with VTE in patients undergoing mastectomy have not been well characterized. To address this we utilized the ACS-NSQIP database to identify and characterize independent risk factors for VTE in 49,028 mastectomy patients. We identified 116 cases of VTE in the 49,028 cases analyzed (0.23%). Obesity (BMI > 30, OR = 1.91, p < 0.001), inpatient status (OR = 3.75, p < 0.001), venous catheterization (OR = 2.67, p = 0.012), prolonged operative time >3 h (OR = 4.36, p < 0.001), and immediate reconstruction (OR = 3.23, p < 0.001) were found to be independent risk factors for VTE. While the incidence of VTE is rare in mastectomy patients, the heightened awareness and increased VTE prophylaxis should be considered in high risk groups.     

Incidence,risk factors and clinical implications of postoperative urinary tract infection in geriatric hip fractures

IntroductionPostoperative urinary tract infection (UTI) is common in geriatric patients; however, little is known about the impact of UTI in orthopedic trauma. The present study was designed to determine the risk factors and clinical impact of postoperative urinary tract infection (UTI) in acute geriatric hip fractures.Patients and methodsGeriatric patients (≥65 years of age) undergoing hip fracture surgery were identified within the American College of Surgeons National Surgical Quality Improvement Program between 2016 and 2019. Patients presenting with UTI at the time of surgery were excluded. Baseline characteristics and outcomes were compared between patients with and without postoperative UTI. Multivariate logistic regression was performed, controlling for potential confounders.ResultsA total of 46,263 patients included in the study. Overall, 1,397 (3.02%) patients had postoperative UTI. Patients who developed postoperative UTI had higher rates of pneumonia (6.44% vs. 3.76%, p < 0.001), DVT (2.22% vs. 1.04%, p < 0.001), sepsis (7.73% vs. 0.62%, p < 0.001), and more frequently experienced postoperative hospital lengths of stay exceeding 6 days (37.94% vs. 20.33%, p < 0.001). Hospital readmission occurred more frequently in patients with postoperative UTI (24.55% vs. 7.85%, p < 0.001), but surprisingly, these patients had a lower mortality rate (1.36% vs. 2.2%, p < 0.001). Adjusted analysis demonstrated the following variables associated with postoperative UTI: age ≥ 85 (OR = 1.37, 95%CI = 1.08 - 1.73), ASA class ≥ 3 (OR = 1.59, 95%CI = 1.21 – 2.08,), chronic steroid use (OR = 1.451, 95%CI = 1.05 - 1.89), blood transfusion (OR = 1.24, 95%CI = 1.05 - 1.48), and >2 days delay from admission to operation (OR = 1.37, 95%CI = 1.05 - 1.79). Postoperative UTI was significantly associated with sepsis (OR = 7.65, 95%CI = 5.72 – 10.21), postoperative length of stay >2 days (OR = 1.83, 95%CI = 1.07 – 3.13), and readmission (OR = 3, 95%CI = 2.54 – 3.55).ConclusionsIn our study, postoperative UTI was found in 3% of geriatric hip fracture patients. Predictors of postoperative UTI were age ≥ 85, ASA class ≥ 3, chronic steroid use, blood transfusion, and time to operation > 2 days from admission. Results showed that postoperative UTI is independently associated with sepsis, postoperative length of stay beyond 2 days, and hospital readmission. To diminish the risk of UTI and its consequences, we recommend operating geriatric hip fractures in 24–48 hours after admission.     

Evaluation of endometrial thickness in hormone receptor positive early stage breast cancer postmenopausal women switching from adjuvant tamoxifen treatment to anastrozole

Evaluation of endometrial thickness by transvaginal ultrasonography (TVUS) in postmenopausal estrogen receptor positive breast cancer patients treated with anastrozole after tamoxifen therapy. This study included 70 postmenopausal estrogen receptor positive breast cancer patients who switched to anastrozole after tamoxifen; patients had endometrial thickness >4 mm and no endometrial malignancy. Endometrial thickness was measured after anastrozole treatment. Endometrial thickness during anastrozole therapy was lower than after tamoxifen therapy (p < 0.001); the mean reduction in endometrial thickness was 4.5 mm (±3.0). Cystic endometrial appearance was more frequent in patients under tamoxifen than in those under anastrozole (p < 0.001). Duration of tamoxifen therapy was not correlated to the endometrial thickness at the time of its suspension. Duration of tamoxifen therapy and endometrial thickness at the time of tamoxifen suspension was correlated to the relative reduction of endometrial thickness during anastrozole therapy. Anastrozole reverses tamoxifen-induced increased endometrial thickness and sonographic endometrial cystic appearance.     

Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data

BackgroundAromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen.MethodsWe analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE.ResultsWe included 47,569 women for the final analysis. Patients were classified into ‘No hormonal treatment (n = 18,807), ‘Switch (n = 2097)’, ‘Tamoxifen (n = 7081)’ and ‘AI (n = 19,584)’. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74–0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84–1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47–0.84).ConclusionsOur results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.     

The impact of both-bone forearm fractures on acute compartment syndrome: An analysis of predisposing factors

ObjectivesAcute compartment syndrome (ACS) is a severe medical condition that, if left untreated, can cause permanent nerve and muscle damage, and may even require amputation. The objective of this study was to identify the risk factors associated with the development of ACS in patients with both-bone fractures of the forearm.MethodsBetween November 2013 and January 2021, a retrospective data collection was conducted on 611 individuals who experienced both-bone forearm fractures at a level 1 trauma center. Among these patients, 78 patients were diagnosed with ACS, while the remaining 533 patients did not have ACS. Based on this division, the patients were categorized into two groups: the ACS group and the non-ACS group. Demographics (including factors such as age, gender, body mass index, crush injury, etc.), comorbidities (including conditions such as diabetes, hypertension, heart disease, anemia, etc.), and admission lab results (including complete blood count, comprehensive metabolic panel, and coagulation profiles, etc.) were analyzed using univariate analysis, logistic regression, and ROC curve analysis.ResultsPredictors of ACS were identified through the final multivariable logistic regression analysis, which revealed that crush injury (p < 0.001, OR = 10.930), the levels of neutrophils (NEU) (p < 0.001, OR = 1.338) and the levels of creatine kinase (CK) (p < 0.001, OR = 1.001) were significant risk factors. Additionally, age (p = 0.045, OR = 0.978) and albumin (ALB) level (p < 0.001, OR = 0.798) were found to provide protective effects against ACS. Furthermore, the receiver operating characteristic (ROC) curve analysis determined cut-off values for NEU and CK to predict ACS: 7.01/L and 669.1 U/L respectively.ConclusionsOur study identified crush injury, NEU, and CK as significant risk factors for ACS in patients with both-bone forearm fractures. We also determined the cut-off values of NEU and CK, allowing for the individualized evaluation of ACS risk and the implementation of early targeted treatments.     

An Open,Randomised, Multicentre,Phase 3 Trial Comparing the Efficacy of Two Tamoxifen Schedules in Preventing Gynaecomastia Induced by Bicalutamide Monotherapy in Prostate Cancer Patients

Background

Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration.

Objective

To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated.

Design, setting, and participants

This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n = 41) and weekly (n = 39). Median follow-up was 24.2 mo.

Intervention

Daily bicalutamide (150 mg) plus daily tamoxifen 20 mg continuously (daily group) or the same but with tamoxifen at 20 mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events.

Measurements

For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires.

Results and limitations

Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p < 0.0001), and it was more severe in patients who switched to weekly tamoxifen (p = 0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p = 0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far.

Conclusions

This study demonstrated that tamoxifen 20 mg/wk is inferior to tamoxifen 20 mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20 mg for the prophylaxis of bicalutamide-induced breast events were confirmed.     

Hip arthroplasty for acute hip fracture in patients with neurological disorders: A report Of 9,702 cases from the Swedish arthroplasty register

IntroductionThe purpose of this study was to investigate neurological disorder as a risk factor for dislocation following arthroplasty for acute hip fractures. We also analysed medical and surgical adverse events (AE), readmission, reoperation, revision, and mortality as secondary outcomes.MethodsA longitudinal cohort study using prospectively collected and aggregated data from the Swedish Hip Arthroplasty Register (SHAR) and the Swedish national patient register. All patients presenting with an acute hip fracture and treated with an arthroplasty in the period from 2005 to 2014 from the SHAR were identified. Patients in receipt of bilateral arthroplasties were excluded. Patients with a relevant pre-existing and diagnosed neurological disorder, as defined by ICD-10 codes, were identified (n = 9,702). All other cases (n = 29,411) were available for logistic regression propensity score matching. Patients were 1:1 matched on age, sex, Charlson comorbidity index, total versus hemiarthroplasty, head size, surgical approach, and year of surgery. Dislocations, adverse events, readmission, reoperation, revision, and mortality were studied using Kaplan-Meier analysis and Cox regression.ResultsThe risk of dislocations was higher for patients with neurological disorder (HR=1.19, CI 1.03- 1.39, p<0.05). Neurological disorder was associated with increased risk of encountering an adverse event (p<0.001 at 90-days); these patients were at higher risk of dying (HR=1.51, CI 1.47–1.56, p<0.001) however they were less likely to be readmitted (HR=0.73, CI 0.70- 0.76, p<0.001). No excess risks of reoperation (HR=1.02, CI 0.90–1.17; p = 0.73) or revision (HR=1.00, CI 0.86–1.17; p = 0.99) were identified in the study group.DiscussionCompared to matched controls, individuals with a preoperatively identified neurological diagnosis had higher rates of mortality, dislocations, and adverse events, but this cohort was not at increased risk of reoperation or revision. This study highlights an area of focus for future research to improve the long-term outcomes in patients with neurological disease undergoing arthroplasty for an acute hip fracture.     

Phantom limb syndrome: Assessment of psychiatric and medical comorbidities associated with Phantom pain in 44,028 below knee amputees

IntroductionPhantom limb syndrome is a debilitating complication after extremity amputation that poses significant challenges to recovery. This study aims to examine the relationship between phantom limb syndrome and mental and physical comorbidities, including a comparison between phantom limb pain and phantom limb syndrome without pain in below knee amputees.MethodsThis is a retrospective cohort study of patients who underwent below knee amputation of the lower extremity in the PearlDiver database, as identified using CPT codes. Analysis was carried out to evaluate the absence or presence of phantom limb syndrome. Matched bivariate analysis accounting for age, sex, Charlson Comorbidity Index score, and region was used to assess whether the presence of pain in phantom limb syndrome patients was associated with increased comorbidity.ResultsIn total, 44,028 patients with below knee amputation were examined: 95% (42,493 patients) did not develop phantom limb syndrome while 4.8% (1,535 patients) of patients did develop phantom limb syndrome. Phantom limb syndrome was significantly associated with increased odds of coexistent major depressive disorder (OR = 1.86, p <0.0001), generalized anxiety disorder (OR = 2.14, p = 0.04), posttraumatic stress disorder (OR = 1.7, p <0.0001), suicidal ideation (OR = 1.62, p <0.0001), obesity (OR = 1.28, p = 0.0007), osteoarthritis (OR = 1.53, p <0.0001), osteoporosis (OR = 1.64, p <0.0001), and low back pain (OR = 2.31, p <0.0001). Analysis of patient cohorts of phantom limb syndrome with pain and those without pain did not reveal a statistically significant relationship between the presence of pain and any dependent variable.ConclusionsThis investigation of over 44,000 patients with below knee amputation revealed that patients with phantom limb syndrome exhibit significantly higher rate of psychiatric comorbidities compared to those without documented phantom limb pain. Suicidal ideation, major depressive disorder, generalized anxiety disorder, and post-traumatic stress disorder were especially common, and consequently a multi-disciplinary approach to management is essential.     

Trends in endocrine therapy prescription and survival in patients with non-metastatic hormone receptor positive breast cancer treated with endocrine therapy: A population based-study

PurposeTo identify prognostic factors of invasive–disease free survival (iDFS) in women with non-metastatic hormone receptor positive (HR+) breast cancer (BC) in daily routine practice.MethodsWe performed a retrospective study using data from the Côte d’Or breast and gynecological cancer registry in France. All women diagnosed with primary invasive non-metastatic HR + BC from 1998 to 2015 and treated by endocrine therapy (ET) were included. Women with bilateral tumors or who received ET for either metastasis or relapse were excluded. We performed adjusted survival analysis and Cox regression to identify prognostic factors of iDFS.ResultsA total of 3976 women were included. Age at diagnosis, ET class, SBR grade, treatment, stage and comorbidity were independently associated with iDFS. Women who had neither surgery nor radiotherapy had the highest risk of recurrence (HR = 3.75, 95%CI [2.65–5.32], p < 0.0001). Receiving aromatase inhibitors (AI) was associated with a lower risk of recurrence (HR = 0.70, 95%CI [0.54–0.90], p = 0.055) compared to tamoxifen. Compared to women with no comorbidities, women with 1 or 2 comorbidities were more likely to receive AI (OR = 1.63, 95%CI [1.22–2.17], p = 0.0009).ConclusionsComorbidities, age at diagnosis and previous treatment were associated with iDFS in non-metastatic HR + BC patients. This study also showed that women who received tamoxifen for their cancer experienced worse iDFS compared to women treated with AI.     

The clinical impact of extrathyroidal extensions on prognoses in pediatric differentiated thyroid cancers

BackgroundThe prognostic impact of extrathyroidal extensions (ETE) on clinical outcomes has not been well studied in pediatric thyroid cancers. The aim of this study was to analyze the clinicopathological characteristics and clinical outcomes according to the extent of ETE in pediatric and adolescent thyroid cancers.MethodsThis study retrospectively reviewed 89 papillary thyroid carcinoma (PTC) patients less than 19 years of age who underwent total thyroidectomy with central neck dissections (CND) between 1997 and 2018. We compared the clinicopathological features among three groups: no ETE, microscopic ETE, and gross ETE.ResultsThe median follow-up time was 111 months. The mean age was 15.3 years and the mean tumor size was 2.4 cm. Tumor sizes larger than 2 cm (OR = 9.2, p = 0.001), exhibited bilaterality (OR = 4.3, p = 0.006), were an aggressive variant (OR = 5.8, p = 0.006), and exhibited central lymph node metastasis (OR = 1.3, p = 0.018), lateral lymph node metastasis (OR = 9.2, p = 0.001), recurrence (OR = 3.9, p = 0.038), and distant metastasis (OR = 4.4, p = 0.016) were associated with gross ETE. There was no remarkable difference in clinicopathological characteristics between the no ETE group and microscopic ETE group, except for aggressive variants (OR = 5.5, p = 0.008). There was a significant difference in recurrence-free survival (RFS) rates according to the extent of ETE (p = 0.025). Furthermore, the distant metastasis-free survival curve presented a significant difference among the three groups (p = 0.018). Both microscopic ETE and gross ETE were significantly associated with worse prognoses in pediatric thyroid cancers.ConclusionsWe recommend that microscopic ETE should be included in the intermediate risk category and that gross ETE should be stratified in the high risk group in future revisions of ATA pediatric guidelines.     

Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials

The meta-analysis was performed to assess the efficacy and safety of daily oral L-arginine and phosphodiesterase type 5 inhibitors (PDE5Is) alone or combination in treating patients with erectile dysfunction (ED). We performed a search of randomised controlled trials in the following databases: PubMed, EMBASE and Cochrane Library databases. Four articles including 373 patients were studied. Erectile functions were significantly improved in three therapy groups compared with baseline. Patients who received the combination of L-arginine and PDE5Is showed significant improvement compared to those treated with L-arginine and PDE5Is alone, as assessed by sexual function index (p <0.00001 and p =0.005, respectively) and total testosterone (p <0.00001 and p =0.0007, respectively). Furthermore, patients who treated with PDE5Is alone exhibited the better efficacy than those treated with L-arginine alone in respects of sexual function index (p <0.00001) and total testosterone (p =0.0001). However, the combination of L-arginine and PDE5Is had no obvious difference relative to PDE5Is alone in terms of various adverse events (AEs). Conclusively, compared with monotherapy, the combination of L-arginine and PDE5Is showed a greater improvement of sexual function and total testosterone, and did not significantly increase the AEs. Besides, PDE5Is alone revealed a better effect than those treated with L-arginine alone for patients with ED.     

The Immunobiogram,a novel in vitro diagnostic test to measure the pharmacodynamic response to immunosuppressive therapy in kidney transplant patients

BackgroundDiagnostic tools to measure the response to individual immunosuppressive drugs for transplant patients are currently lacking. We previously developed the blood-based Immunobiogram bioassay for in-vitro characterization of the pharmacodynamic response of patients' own immune cells to a range of immunosuppressants. We used Immunobiogram to examine the association between patients' sensitivity to their prescribed immunosuppressants and clinical outcome.MethodsWe conducted an international, multicenter, observational study in a kidney transplant population undergoing maintenance immunosuppressive therapy. Patients were selected by clinical course poor [PCC] N = 53 (with renal dysfunction, and rejection signs in biopsy or/and an increase in DSA strength in last 12 months) versus good [GCC] N = 50 (with stable renal function and treatment, no rejection and no DSA titers). Immunobiogram dose-response curve parameters were compared between both subgroups in patients treated with mycophenolate, tacrolimus, corticosteroids, cyclosporine A or everolimus. Parameters for which significant inter-group differences were observed were further analyzed by univariate and subsequent multivariate logistic regression.ResultsClinical outcome was associated with following parameters: area over the curve (AOC) and 25% (ID25) and 50% (ID50) inhibitory response in mycophenolate, tacrolimus, and corticosteroid-treated subgroups, respectively. These statistically significant associations persisted in mycophenolate (OR 0.003, CI95% <0.001–0.258; p = 0.01) and tacrolimus (OR < 0.0001, CI95% <0.00001–0.202; p = 0.016) subgroups after adjusting for concomitant corticosteroid treatment, and in corticosteroid subgroup after adjusting for concomitant mycophenolate or tacrolimus treatment (OR 0.003; CI95% <0.0001–0.499; p = 0.026).ConclusionsOur results highlight the potential of Immunobiogram as a tool to test the pharmacodynamic response to individual immunosuppressive drugs.     

Identification of concomitant injuries associated with specific spine level fractures in polytrauma patients

IntroductionSpine fractures are associated with high energy mechanisms and can lead to substantial morbidity and mortality in the trauma setting. Rapid identification and treatment of these fractures and their associated injuries are paramount in preventing adverse outcomes. The purpose of this study is to identify concomitant skeletal and non-skeletal injuries related to cervical, thoracic, and lumbar fractures.MethodsA retrospective review of institutional American College of Surgeons (ACS) registry was conducted on 3,399 consecutive trauma patients identifying those with spine fractures from 1/2016–12/2019. Two-hundred ninety patients were included(8.5%) and separated into three groups based on fracture location: eighty-eight cervical(C)-spine, 129thoracic(T)-spine, and 143lumbar(L)-spine. Logistic regression analyses were performed to identify associated injuries, presenting injury severity score(ISS) and Glasgow coma scale(GCS), mechanism of injury, demographic data, substance use, and paralysis for each group. Cox hazard regression was utilized to identify factors associated with inpatient mortality.ResultsC-spine fractures were associated with head trauma(OR2.18,p = 0.003),intracranial bleeding (OR2.64,p = 0.001),facial(OR2.25,p = 0.02) and skull fractures(OR3.92,p = 0.001),and cervical cord injuries(OR4.78,p = 0.012). T-spine fractures were associated with rib fractures(OR2.31,p = 0.003). L-spine fractures were associated with rib(OR1.77, p = 0.04), pelvic(OR5.11,p<0.001), tibia/fibula (OR2.31,p = 0.05), and foot/ankle fractures(OR3.32,p = 0.04), thoracic(OR2.43,p = 0.008) and retroperitoneal cavity visceral injuries(OR27.3,p = 0.001). Falls≤6meters were also significantly associated with C-spine fractures(OR1.70,p = 0.04) while falls>6meters were associated with L-spine fractures(OR4.30,p = 0.001). Inpatient mortality risk increased in patients with C-spine fractures(HR4.41,p = 0.002), higher ISS(HR1.05, p<0.001), and lower GCS(HR0.85,p<0.001). Last, patients≥65-years-old were more likely to experience C-spine fractures(OR1.88,p = 0.03).ConclusionPatients who experience fractures of the cervical, thoracic, or lumbar spine are at risk for additional fractures, visceral injury, and/or death. Awareness of the associations between spinal fractures and other injuries can increase diagnostic efficacy, improve patient care, and provide valuable prognostic information. These associations highlight the importance of effective and timely communication and multidisciplinary collaboration.     

Enhancing recovery after minimally invasive surgery in children: A systematic review of the literature and meta-analysis

ObjectiveEnhanced recovery after surgery (ERAS) has been widely implemented after minimally invasive surgeries (MIS) in adults. The aim of this study was to evaluate the current evidence available on ERAS after MIS in children.MethodsUsing a defined search strategy (PubMed, Cochrane, Scopus), we performed a systematic review of the literature, searching for studies reporting on ERAS after MIS (thoracoscopy, laparoscopy, retroperitoneoscopy) in children (1975–2019). This study was registered with PROSPERO-international prospective register of systematic reviews. A meta-analysis was conducted using comparative studies for length of stay (LOS), complication rates, and readmission rates.ResultsOf 180 abstracts screened, 20 full-text articles were analyzed, and 9 were included in our systematic review (1 randomized controlled trial, 3 prospective, and 5 retrospective studies), involving a total number of 531 patients. ERAS has been applied to laparoscopy for digestive (n = 7 studies) or urologic surgeries (n = 1), as well as thoracoscopy (n = 1). Mean LOS was decreased in ERAS children compared to controls (6 studies, −1.12 days, 95%IC: −1.5 to −0.82, p < 0.00001). There was no difference in complication rates between ERAS children and control children (5 studies, 13% vs 14%, OR = 0.84, 95%CI: 0.49–1.44, p = 0.52). The 30-day readmission rate was decreased in ERAS children compared to controls (6 studies, 4% vs 10%, OR = 0.34, 95%CI: 0.18–0.66, p = 0.001).ConclusionsAlthough the evidence regarding ERAS in MIS is scarce, these protocols seem safe and effective, by decreasing LOS and 30-day readmission rate, without increasing post-operative complication rates.     

Influencing factors for the recurrence of diabetic foot ulcers: A meta-analysis

This study aims to systematically review and identify the related influencing factors for the recurrence of diabetic foot ulcers (DFUs)in diabetic patients. We searched PUBMED, EMBASE, Web of Science, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wan Fang and VIP databases to identify eligible studies published before March 31, 2022 to collect case–control studies or cohort studies on the related influencing factors for the recurrence of DFUs. Two reviewers independently screened the literature, and extracted data. Also, they assessed the risk of bias of the included studies using the Newcastle-Ottawa Scale. A meta-analysis was performed using RevMan5.4.1 software. 20 studies were included; 4238 patients were enrolled, in which 1567 were in the DFU recurrence group and 2671 were in the non-recurrent DFU group. Risk factors for the recurrence of DFUs included diabetic peripheral neuropathy (odds ratio [OR] = 4.05, 95% CI, 2.50-6.58, P < 0.00001), peripheral vascular disease (OR = 3.94, 95% CI, 2.65-5.84, P < 0.00001), poor blood glucose control (OR = 3.27, 95% confidence interval [CI], 2.79-3.84, P < 0.00001), plantar ulcer (OR = 3.66, 95% CI, 2.06-6.50, P < 0.00001), osteomyelitis (OR = 7.17, 95% CI, 2.29-22.47, P = 0.0007), smoking (OR = 1.98, 95% CI, 1.65-2.38, P < 0.00001), history of amputation (OR = 11.96, 95%CI, 4.60-31.14, P < 00001), multidrug-resistant bacterial infection (OR = 3.61, 95%CI, 3.13-4.17, P < 0.00001), callus (OR = 5.70, 95%CI, 1.36-23.89, P = 0.02), previous diabetic foot ulcer (OR = 4.10, 95% CI, 2.58-6.50, P < 0.00001), duration of previous diabetic foot ulcer >60d (OR = 1.02, 95% CI, 1.00-1.03, P = 0.004), history of vascular intervention (OR = 3.20, 95% CI, 2.13-4.81, P < 0.00001) and Wagner grade III/IV (OR = 4.40, 95% CI, 2.21-8.78, P < 0.0001). However, no significant differences were found in age, duration of diabetes, body mass index, total cholesterol or foot deformity. Recurrence of diabetic foot ulcers is affected by a variety of factors. Thus, we should focus on high-risk groups and take targeted interventions as soon as possible to reduce the recurrence rate of DFUs, because of the limited quality and quantity of the included studies, more rigorous studies with adequate sample sizes are needed to verify the conclusion.     

Aromatase inhibitors alone or sequentially combined with tamoxifen in postmenopausal early breast cancer compared with tamoxifen or placebo – Meta-analyses on efficacy and adverse events based on randomized clinical trials

Tamoxifen (TAM) and aromatase inhibitors (AI) are adjuvant therapy options for postmenopausal women with estrogen receptor positive (ER+) breast cancer. This systematic review of seven randomized controlled studies comparing TAM and AI, and one study comparing extended therapy with an AI with placebo after about 5 years of tamoxifen, aims to assess long-term clinical efficacy and adverse events. The literature review was performed according to the principles of the Cochrane Collaboration. The search included common databases up to 2013-01-14. Studies of high or moderate quality were used for grading of evidence. Revman™ software was utilized for meta-analyses of published data. Disease free survival (DFS) and overall survival (OS) were improved with AI monotherapy compared to TAM with high and moderate quality of evidence respectively. Sequenced therapy with AI → TAM (or vice versa) improved DFS compared with TAM with moderate quality of evidence, but did not improve OS (low quality of evidence). However, if only studies on sequenced AI therapy with randomization before endocrine therapy were considered, no improvement of DFS could be found. Fractures are more frequently associated with AI whereas the risk of endometrial cancer and venous thromboembolism are higher with TAM. For cardiovascular events no difference was found between AI (mono- or sequenced therapy) and TAM, whereas sequenced therapy compared with AI had lower risk of cardiovascular events (moderate level of evidence).AIs are superior to TAM as adjuvant hormonal therapy for postmenopausal ER-positive breast cancer. TAM can be considered for individual patients due to the different toxicity profile compared with AI. Cardiovascular events related to AI treatment deserve further attention.     

A look at racial and socioeconomic disparities in post-mastectomy breast reconstruction at a midwestern academic hospital

Purpose of this study was to assess likelihood of undergoing breast reconstruction based on race, socioeconomic status, insurance, and distance from the hospital. Patients with public insurance were less likely to undergo reconstruction than patients with private insurance (OR = 2.99, p < 0.001). White patients were more likely to undergo reconstruction (OR = 0.62, p = 0.02). Patients who lived 10–20 miles and 20–40 miles from UCMC were more likely to undergo reconstruction (OR = 1.93, p = 0.01; OR = 3.06, p < 0.001). White patients and patients with private insurance are disproportionately undergoing breast reconstruction after mastectomy.     

Aromatase inhibitors in the adjuvant treatment of postmenopausal women with early breast cancer: Putting safety issues into perspective

Tamoxifen has been the gold standard adjuvant therapy for the treatment of postmenopausal women with hormone-receptor-positive (HR+) early breast cancer for many years. Tamoxifen treatment is limited to 5 years because of the development of de novo and acquired resistance, and an ongoing risk of adverse events, including endometrial cancer, thromboembolic events, and gynecological symptoms with long-term use. The third-generation aromatase inhibitors (AIs), letrozole, anastrozole, and exemestane, are displacing tamoxifen as the first-choice therapy for HR+ early breast cancer, and are now recommended as the preferred therapy by national and international guidelines. Recent randomized trials have demonstrated that the AIs are more effective than tamoxifen in preventing disease recurrence when used in substitution and sequential strategies in the early adjuvant setting, and letrozole has been shown to be more effective than placebo in the extended adjuvant setting (after 5 years of tamoxifen therapy). Trial safety data show that the overall tolerability of AIs is similar to that of tamoxifen, with adverse events being predictably characteristic of estrogen deprivation; however, some important differences in adverse event profiles between tamoxifen and the AIs have been demonstrated. In addition to antiestrogenic effects, tamoxifen acts as an estrogen agonist in some tissues, which can lead to serious side effects not associated with the AIs, which prevent estrogen biosynthesis. A lower incidence of gynecological and thromboembolic events is observed in patients taking AIs, and fewer cases of endometrial cancer are seen compared with tamoxifen. Adverse events that are more frequent with adjuvant AI therapy compared with tamoxifen include arthralgia and myalgia, bone loss, and effects on the cardiovascular system and blood lipids. The effects of AIs on bone are predictable and may be easily managed, where necessary, with bisphosphonates. Studies examining the effects of AIs on the cardiovascular system and lipid profiles, including in the extended adjuvant setting, suggest that these adverse events may be due to the absence of a protective effect of tamoxifen rather than true AI toxicity. Further studies are required to determine the long-term safety of AI therapy in postmenopausal women with HR+ early breast cancer.     

Metastatic breast cancer subtypes and central nervous system metastases

BackgroundBreast cancer (BC) subtypes have different survival and response to therapy. We studied predictors of central nervous system metastases (CNS-M) and outcome after CNS-M diagnosis according to tumor subtype.Patients and methods488 patients with diagnosis of metastatic BC were retrospectively evaluated. According to the combination of hormone receptors (HR) and HER2 status, tumors were grouped in: Luminal (Lum), Luminal/HER2+, pure HER2-positive (pHER2+) and triple negative (TN). Time to CNS progression, CNS-M free interval and Overall Survival (OS) after CNS-M occurrence were compared by the log-rank test. Cox-proportional hazard models were used to study predictor factors associated with CNS progression, including tumor subtype and all potentially clinical relevant variables.Results115 patients (pts) developed CNS-M with a median time to CNS progression of 31 months. The rate of CNS-M by subtype was: Lum 14%, Lum/HER2+ 35%, pHER2+ 49%, TN 22% (p < 0.001). Compared with Lum tumors, Lum/HER2+ (HR 2.514, p < 0.001), pHER2+ (HR 6.799, p < 0.0001) and TN (HR = 3.179, p < 0.001) subtypes were at higher risk of CNS-M. Median OS in months after CNS-M was: Lum 7.4, Lum/HER2+ 19.2, pHER2+ 7, TN 4.9 (p < 0.002). Belonging to the Lum/HER2+ subtype (HR 0.48, p < 0.037) and having isolated CNS (HR 0.37, p < 0.004) predicted significantly reduced risk of death.ConclusionsAfter CNS-M, the Lum/HER2+ subtype appears associated with the longest OS. Prospective clinical trials would be required for evaluating the potential role of screening for asymptomatic CNS lesions and of more aggressive CNS-M treatment in Lum/HER2+ subtype.