Impact of inhalation injury on outcomes in critically ill burns patients: 12-year experience at a regional burns centre

IntroductionBurns inhalation injury increases the attributable mortality of burns related trauma. However, diagnostic uncertainties around bronchoscopically graded severity, and its effect on outcomes, remain. This study evaluated the impact of different bronchoscopic burns inhalation injury grades on outcomes.MethodsA single-centre cohort study of all patients admitted to the London Burns centre intensive care unit (BICU) over 12 years. Demographic data, burn and burns inhalation injury characteristics, and ICU-related parameters were collected retrospectively. The primary outcome was mortality. Secondary outcomes were hospital and ICU lengths of stay. The impact of pneumonia was determined. Univariate and multivariable Cox’s proportional hazards regression analyses informed factors predicting mortality.ResultsBurns inhalation injury was diagnosed in 84 of 231 (36%) critically ill burns patients; 20 mild (grade 1), 41 severe (grades 2/3) and 23 unclassified bronchoscopically. Median (IQR) total body surface area burned (TBSA) was 20% (10?40). Mortality was significantly higher in patients with burns inhalation injury vs those without burns inhalation injury (38/84 [45%] vs 35/147 [24%], p < 0.001). Patients with pneumonia had a higher mortality than those without (34/125 [27%] vs 8/71 [11%], p = 0.009). In multivariable analysis, severe burns inhalation injury significantly increased mortality (adjusted HR=2.14, 95%CI: 1.12–4.09, p = 0.022), compared with mild injury (adjusted HR=0.58, 95% CI: 0.18–1.86, p = 0.363). Facial burns (adjusted HR=3.13, 95%CI: 1.69–5.79, p < 0.001), higher TBSA (adjusted HR=1.05, 95%CI: 1.04–1.06, p < 0.001) and older age (adjusted HR=1.04, 95%CI: 1.02–1.07, p < 0.001) also independently predicted mortality, though pneumonia did not.ConclusionsSevere burns inhalation injury is a significant risk factor for mortality in critically ill burns patients. However, pneumonia did not increase mortality from burns inhalation injury. This work confirms prior implications of bronchoscopically graded burns inhalation injury. Further study is suggested, through registries, into the diagnostic accuracy and reliability of bronchoscopy in burns related lung injury.     

Prolonged Mechanical Ventilation After Lung Transplantation—A Single‐Center Study

This single‐center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82–21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42–31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86–16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98–12.81], p = 0.001), among others. Overall 1‐year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long‐term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40–5.25], p < 0.001), post‐LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06–5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39–2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in‐hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.     

Does mortality after trauma team activation peak at shift change?

BackgroundPrior institutional data have demonstrated trauma mortality to be highest between 06:00–07:59 at our center, which is also when providers change shifts (07:00–07:30). The objective was definition of patient, provider, and systems variables associated with trauma mortality at shift change among patients arriving as trauma team activations (TTA).MethodsAll TTA patients at our ACS-verified Level I trauma center were included (01/2008–07/2019), excluding those with undocumented arrival time. Study groups were defined by arrival time: shift change (SC) (06:00–07:59) vs. non-shift change (NSC) (all other times). Univariable/multivariable analyses compared key variables. Propensity score analysis compared outcomes after matching.ResultsAfter exclusions, 6020 patients remained: 229 (4%) SC and 5791 (96%) NSC. SC mortality was 25% vs. 16% during NSC (p < 0.001). More SC patients arrived with SBP <90 (19% vs. 11%, p < 0.001) or GCS <9 (35% vs. 24%, p < 0.001). ISS was higher during SC (43[32–50] vs. 34[27–50], p < 0.001). Time to CT scan (36[23–66] vs. 38[23–61] minutes, p = 0.638) and emergent surgery (94[35–141] vs. 63[34–107] minutes, p = 0.071) were comparable. Older age (p < 0.001), SBP <90 (p < 0.001), GCS <9 (p < 0.001), need for emergent operative intervention (p = 0.044), and higher ISS (p < 0.001) were independently associated with mortality. After propensity score matching, mortality was no different between SC and NSC (p = 0.764).ConclusionsEarly morning is a low-volume, high-mortality time for TTAs. Increased mortality at shift change was independently associated with patient/injury factors but not provider/systems factors. Ensuring ample clinical resource allocation during this high acuity time may be prudent to streamline patient care at shift change.     

Factors influencing short‐ and long‐term mortality after lower limb amputation

Mortality after lower limb amputation is high, with UK 30‐day mortality rates of 9–17%. We performed a retrospective analysis of factors affecting early and late outcome after lower limb amputation for peripheral vascular disease or diabetic complications at a UK tertiary referral vascular centre between 2003 and 2010. Three hundred and thirty‐nine patients (233 male), of median (IQR [range]) age 73 (62–79 [26–92]) years underwent amputation. Thirty‐day mortality was 12.4%. On regression modelling, the risk of 30‐day mortality was increased in patients of ASA grade ≥ 4 (OR 4.23, 95% CI 2.07–8.63), p < 0.001 and age between 74 and 79 years (OR 3.8, 95% CI 1.10–13.13), p = 0.04 and older than 79 years (OR 4.08, 95% CI 1.25–13.25), p = 0.02. Peri‐operative (30‐day) mortality for these groups was 23.2%, 13.7% and 18.8%, respectively. Survival and Cox regression analysis demonstrated that long‐term mortality was associated with: age 74–79 years (HR 2.15, 95% CI 1.38–3.35), p = 0.001; age > 79 years (HR 2.78, 95% CI 1.82–4.25), p < 0.001; ASA grade ≥ 4 (HR 2.04, 95% CI 1.51–2.75), p < 0.001; out‐of‐hours operating (HR 1.51, 95% CI 1.08–2.10), p = 0.02; and chronic kidney disease stage 4–5 (1.57, 95% CI 1.07–2.30), p = 0.02. Anaesthetic technique was associated with long‐term mortality on survival analysis (p = 0.04), but not when analysed using regression modelling. Mortality after lower limb amputation relates to patient age, ASA, out‐of‐hours surgery and renal dysfunction. These data support lower limb amputations’ being performed during daytime hours and after modification of correctable risk factors.     

Usefulness of lactate albumin ratio at admission to predict 28-day mortality in critically ill severely burned patients: A retrospective cohort study

IntroductionLactate albumin ratio (LAR) has been used as a prognostic marker associated with organ failure in critically ill septic patients. LAR and its association with outcomes has never been studied in burned patients. The aim of this study was to evaluate the ability of LAR to predict 28-day mortality.MethodsA retrospective cohort study including all burn patients hospitalized in intensive care unit. The primary endpoint was the 28-day mortality.ResultsOne thousand three hundred thirty four patients were screened, and 471 were included between June 2012 and December 2018. Briefly, the population study was mainly composed by men (249, 59.1%), the median age, TBSA burned, full thickness, ABSI and IGS2 were 52 [34–68], 20 [10–40], 8 [1–23], 7 [5–9] and 25 [15–40] respectively. Fifty-two patients (12.4%) died at day 28 after admission. At admission, the LAR level was lower in 28-day survivors compared non-survivors (0.05 [0.04, 0.08] vs 0.12 [0.07, 0.26], p < 0.001 respectively). In multivariate analysis accounting for ABSI, LAR levels at admission> 0.13 was independently associated with 28-day mortality (adjusted OR = 3.98 (IC95 1.88–8.35)). The ability of LAR at admission to discriminate 28-day mortality showed an AUC identical when compared to SOFA and ABSI scores (0.81 (IC95 0.74–0.88), 0.80 (IC95 0.72–0.85) and (0.85 (IC95 0.80–0.90), p < 0.05, respectively). Patients with LAR levels ≥ 0.13 at admission had higher 28-day mortality (40.6% vs 6.8%, p < 0.001, HR 7.39 (IC95 4.28–12.76)).ConclusionAt admission, LAR is an easy and reliable marker independently associated to 28-day mortality in patients with severe burn injury, but prediction by LAR does not perform better than lactate level alone     

Male breast cancer: Looking for better prognostic subgroups

PurposeMale Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted.Patients/methodsRetrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel.ResultsAccording to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size >2 cm (HR:1.8; 95%CI:1.0–3.4years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7–14.3years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2–3.1years, p < 0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2–16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6–7.8 years).ConclusionFBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.     

Post‐transplant lymphoproliferative disorder after pancreas transplantation: a United Network for Organ Sharing database analysis

There are not a great deal of data on post‐transplant lymphoproliferative disorder (PTLD) following pancreas transplantation. We analyzed the United Network for Organ Sharing national database of pancreas transplants to identify predictors of PTLD development. A univariate Cox model was generated for each potential predictor, and those at least marginally associated (p < 0.15) with PTLD were entered into a multivariable Cox model. PTLD developed in 43 patients (1.0%) of 4205 pancreas transplants. Mean follow‐up time was 4.9 ± 2.2 yr. In the multivariable Cox model, recipient EBV seronegativity (HR 5.52, 95% CI: 2.99–10.19, p < 0.001), not having tacrolimus in the immunosuppressive regimen (HR 6.02, 95% CI: 2.74–13.19, p < 0.001), recipient age (HR 0.96, 95% CI: 0.92–0.99, p = 0.02), non‐white ethnicity (HR 0.11, 95% CI: 0.02–0.84, p = 0.03), and HLA mismatching (HR 0.80, 95% CI: 0.67–0.97, p = 0.02) were significantly associated with the development of PTLD. Patient survival was significantly decreased in patients with PTLD, with a one‐, three‐, and five‐yr survival of 91%, 76%, and 70%, compared with 97%, 93%, and 88% in patients without PTLD (p < 0.001). PTLD is an uncommon but potentially lethal complication following pancreas transplantation. Patients with the risk factors identified should be monitored closely for the development of PTLD.     

Recipient body mass index and age interact to impact survival after heart transplantation

Although recipient body mass index (BMI) and age are known risk factors for mortality after heart transplantation, how they interact to influence survival is unknown. Our study utilized the UNOS registry from 1997 to 2012 to define the interaction between BMI and age and its impact on survival after heart transplantation. Recipients were stratified by BMI: underweight (<18.5), normal weight (18.5–24.99), overweight (25–29.99), and either moderate (30–34.99), severe (35–39.99), or very severe (≥40) obesity. Recipients were secondarily stratified based on age: 18–40 (younger recipients), 40–65 (reference group), and ≥65 (advanced age recipients). Among younger recipients, being underweight was associated with improved adjusted survival (HR 0.902; p = 0.010) while higher mortality was seen in younger overweight recipients (HR 1.260; p = 0.005). However, no differences in adjusted survival were appreciated in underweight and overweight advanced age recipients. Obesity (BMI ≥ 30) was associated with increased adjusted mortality in normal age recipients (HR 1.152; p = 0.021) and even more so with young (HR 1.576; p < 0.001) and advanced age recipients (HR 1.292; p = 0.001). These results demonstrate that BMI and age interact to impact survival as age modifies BMI–mortality curves, particularly with younger and advanced age recipients.     

Differences in sensitivity to neoadjuvant chemotherapy among invasive lobular and ductal carcinoma of the breast and implications on surgery–A systematic review and meta-analysis

Meta-analysis of >87,000 patients demonstrates that patients with invasive lobular carcinoma of the breast are far less likely to achieve pCR of the breast or axilla compared to their ductal counterparts, receive less BCS and more frequently return positive margins.BackgroundNeoadjuvant chemotherapy (NACT) facilitates tumour downstaging, increases breast conserving surgery (BCS) and assesses tumour chemosensitivity. Despite clinicopathological differences in Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC), decision making surrounding the use NACT does not take account of histological differences.AimTo determine the impact NACT on pathological complete response (pCR), breast conserving surgery (BCS), margin status and axillary pCR in ILC and IDC.MethodsA systematic review was performed in accordance with the PRISMA guidelines. Studies reporting outcomes among ILC and IDCs following NACT were identified. Dichotomous variables were pooled as odds ratios (ORs) with 95% confidence intervals_(CI) using the Mantel-Haenszel method. P-values <0.05 were statistically significant.Results40 studies including 87,303 (7596 ILC [8.7%]and 79,708 IDC [91.3%]) patients were available for analysis. Mean age at diagnosis was 54.9 vs. 50.9 years for ILC and IDC, respectively. IDCs were significantly more likely to achieve pCR (22.1% v 7.4%, OR: 3.03 [95% CI 2.5–3.68] p < 0.00001), axillary pCR (23.6% vs. 13.4%, OR: 2.01 [95% CI 1.77–2.28] p < 0.00001) and receive BCS (45.7% vs. 33.3%, OR 2.14 [95% CI 1.87–2.45] p < 0.00001) versus ILCs. ILCs were significantly more likely to have positive margins at the time of surgery (36% vs 13.5%, OR 4.84 [95% CI 2.88–8.15] p < 0.00001).ConclusionThis is the largest study comparing the impact of NACT among ILC and IDC with respect to pCR and BCS. ILC has different outcomes to IDC following NACT and incorporate it into treatment decisions and future clinical guidelines.     

The impact of young age at diagnosis (age <40 years) on prognosis varies by breast cancer subtype: A U.S. SEER database analysis

PurposeWomen under 40 years old are at increased risk for developing human epidermal growth factor receptor 2 (HER2) positive or triple negative subtype and more advanced breast cancer, yet young age itself has also historically been an independent prognostic factor.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) Program, we examined data for 271,173 women with stage I-III breast cancer between 2010 and 2015. Using Fine and Gray regression models to account for competing risks, we examined the risk of breast cancer-specific death by age and clinical subtypes, considering grade, hormone receptor (HR) and HER2 status, adjusting for demographic, clinical and treatment variables.ResultsOf 271,173 women eligible for analysis, 14,109 were <40 years of age. Women under 40 years old were more likely to be non-white, uninsured, and to have higher stage, higher grade, HER2-positive and triple-negative subtype disease (all, p < 0.001). Compared to women ages 40–60, women ages <40 had higher breast cancer mortality (hazard ratio, 1.8; 95% confidence interval (CI) 1.6–1.9) in unadjusted analysis. In models controlling for demographic, clinical and treatment factors, young age was significantly associated with an increased risk of breast cancer mortality among women with HR-positive, lower grade disease (hazard ratio 1.7; 95% CI 1.4–2.1) but not for women with high grade/HR-positive, HER2-positive, or triple-negative disease. Women age >75 had increased breast cancer mortality in all subtypes.ConclusionWith modern clinical subtyping, age under 40 remains independently associated with worse outcomes in 30 months follow-up only in HR-positive, lower grade disease.     

Age related differences in primary testicular lymphoma: A population based cohort study

IntroductionPrimary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50.MethodsThe SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared.ResultsThere was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1–50), and 72 (IQR 51–95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57–0.71) and 0.34 (95% CI: 0.31–0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25–6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26–0.40) compared to HR of 0.40 (95% CI: 0.37–0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05– 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM.ConclusionsPTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.     

Survival of south african women with breast cancer receiving anti-retroviral therapy for HIV

PurposeBreast cancer outcomes in sub-Saharan Africa is reported to be poor, with an estimated five-year survival of 50% when compared to almost 90% in high-income countries. Although several studies have looked at the effect of HIV in breast cancer survival, the effect of ARTs has not been well elucidated.MethodsAll females newly diagnosed with invasive breast cancer from May 2015–September 2017 at Charlotte Maxeke Johannesburg Academic and Chris Hani Baragwanath Academic Hospital were enrolled. We analysed overall survival and disease-free survival, comparing HIV positive and negative patients. Kaplan-Meier survival curves were generated with p-values calculated using a log-rank test of equality while hazard ratios and their 95% confidence intervals (CIs) were estimated using Cox regression models.ResultsOf 1019 patients enrolled, 22% were HIV positive. The overall survival (95% CI) was 53.5% (50.1–56.7%) with a disease-free survival of 55.8% (52.1–59.3) after 4 years of follow up. HIV infection was associated with worse overall survival (HR (95% CI): 1.50 (1.22–1.85), p < 0.001) and disease-free survival (OR (95% CI):2.63 (1.71–4.03), p < 0.001), especially among those not on ART at the time of breast cancer diagnosis. Advanced stage of the disease and hormone-receptor negative breast cancer subtypes were also associated with poor survival.ConclusionHIV infection was associated with worse overall and disease-free survival. HIV patients on ARTs had favourable overall and disease-free survival and with ARTs now being made accessible to all the outcome of women with HIV and breast cancer is expected to improve.     

Decreased Incidence of Hirschsprung-Associated Enterocolitis During COVID-19 Across United States Children's Hospitals

BackgroundThe Coronavirus Disease 2019 pandemic provided a natural experiment to study the effect of social distancing on the risk of developing Hirschsprung's Associated Enterocolitis (HAEC).MethodsUsing the Pediatric Health Information System (PHIS), a retrospective cohort study of children (<18 years) with Hirschsprung's Disease (HSCR) across 47 United States children's hospitals was performed. The primary outcome was HAEC admissions per 10,000 patient-days. The exposure (COVID-19) was defined as April 2020–December 2021. The unexposed (historical control) period was April 2018–December 2019. Secondary outcomes included sepsis, bowel perforation, intensive care unit (ICU) admission, mortality, and length of stay.ResultsOverall, we included 5707 patients with HSCR during the study period. There were 984 and 834 HAEC admissions during the pre-pandemic and pandemic periods, respectively (2.6 vs. 1.9 HAEC admissions per 10,000 patient-days, incident rate ratio [95% confidence interval]: 0.74 [0.67, 0.81], p < 0.001). Compared to pre-pandemic, those with HAEC during the pandemic were younger (median [IQR]: 566 [162, 1430] days pandemic vs. 746 [259, 1609] days pre-pandemic, p < 0.001) and more likely to live in the lowest quartile of median household income zip codes (24% pandemic vs. 19% pre-pandemic, p = 0.02). There were no significant differences in rates of sepsis (6.1% pandemic vs. 6.1% pre-pandemic, p > 0.9), bowel perforation (1.3% pandemic vs. 1.2% pre-pandemic, p = 0.8), ICU admissions (9.6% pandemic vs. 12% pre-pandemic, p = 0.2), mortality (0.5% pandemic vs. 0.6% pre-pandemic, p = 0.8), or length of stay (median [interquartile range]: 4 [(Pastor et al., 2009; Gosain and Brinkman, 2015) 2,112,11 days pandemic vs. 5 [(Pastor et al., 2009; Tang et al., 2020) 2,102,10 days pre-pandemic, p = 0.4).ConclusionsThe COVID-19 pandemic was associated with significantly decreased incidence of HAEC admissions across US children's hospitals. Possible etiologies such as social distancing should be explored.Level of evidenceII.     

Breast cancer in octogenarian. Are we doing our best? A population-registry based study

BackgroundThe number of old people with breast cancer is estimated to increase during the next years in developed countries. However, management of breast cancer in octogenarians is not well established. The main objective was to evaluate if patients older than 80 years with breast cancer are receiving the most convenient treatment by using a population registry cancer analysis.Patients and methodsA retrospective analysis of a population cancer registry was designed. Data were retrieved from the Castellon Cancer Registry (Valencian Community, Spain). Patient records were analyzed from January 1, 1995 to December 31, 2013. Two groups were defined: group A, <80 years; and group B, >= 80 years. Survival analyses were sequentially performed into three phases. First, a non-adjusted Kaplan Meier analysis was conducted. For the second survival analyses, Cox's proportional hazards model of Overall survival was used adjusting for condensed-TNM stage and adjuvant treatments. Finally, the third specific adjustment was carried out adding information of life expectancy by age for Spanish women, corresponding to year 2008 with condensed-TNM stage and Propensity Score variable, as an approximation to relative or disease-specific survival.ResultsThe total number of included patients was 1304. Women ≥80 years presented a more extended disease, larger tumors and less in situ carcinomas. A lower proportion of women ≥80 years received adjuvant therapies. In the absence of any adjustment of results, the overall survival in women ≥80 years was poorer than in younger patients (median of 14.1 years for <80y vs. 5.7 years for ≥80y), the crude HR was 4.6 (95% CI: 2.9–7.5) p < 0.001. For second survival analysis, the HR was 2.5 (95% CI: 1.8–3.5) p < 0.001. After the third adjustment the HR was 1.7 (95% CI: 1.2–2.4) p = 0.004.ConclusionsOctogenarians with operable breast cancer are receiving suboptimal treatments, which can have repercussions on survival. New studies are required to identify a subgroup of women age ≥80 years who may benefit from more aggressive treatment and a population of older women on the basis of tumor characteristics, comorbidities and life expectancy who may not need as aggressive treatment.     

Trends in surgery and survival for T1-T2 male breast cancer: A study from the National Cancer Database

BackgroundDespite evidence that early-stage male breast cancer (MBC) can be treated the same as in females, we hypothesized that men undergo more extensive surgery.MethodsPatients with clinical T1-2 breast cancer were identified in the National Cancer Database 2004–2016. Trends in surgery type and overall survival were compared between sexes.ResultsOf 9,782 males and 1,078,105 females, most were cN0 with AJCC stage I/II disease. Unilateral mastectomy was most common in men (67.1% vs. 24.1%, p < 0.001) and partial mastectomy in women (64.7% vs. 26.4%, p < 0.001), with no significant change over time. Over 1/3 of men received ALND in 2016. While overall survival was superior in females (HR 0.83, 95% CI 0.73–0.94, p = 0.003), partial mastectomy was associated with a 42% reduction in mortality risk for males (HR 0.58, 95% CI 0.4–0.8, p = 0.003).ConclusionsDe-escalation of surgery could be considered for MBC to improve survival and align with current standards of care.     

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis

ImportanceCarboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial.MethodsThe study was prospectively registered at PROSPERO (CRD42021228386).We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes.ResultsEight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I² 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I² 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44–3.08; I² 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm.Conclusionand relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.     

Utilization of an Enhanced Recovery After Surgery (ERAS) protocol for pediatric metabolic and bariatric surgery

IntroductionEnhanced recovery after surgery (ERAS) protocols for pediatric metabolic and bariatric surgery are limited. In 2018, an ERAS protocol for patients undergoing robotically assisted vertical sleeve gastrectomy (r-VSG) was instituted. This study's aim was to compare outcomes before and after ERAS initiation.MethodsA single institution retrospective review of patients undergoing r-VSG from July 2015 to July 2021 was performed. The multimodal ERAS protocol focused on limiting post-operative nausea and narcotic utilization. Subjects were categorized into non-ERAS (July 2015–July 2018) and ERAS (August 2018–July 2021) groups. In-hospital and 30-day outcomes were compared.Results110 subjects (94 females) with a median age of 17.6 years (range 12.5–22.0 years) were included (60 non-ERAS, 50 ERAS). Demographics were similar except for a higher proportion of females in the non-ERAS group (97% vs 72%, p < 0.001). A significant decrease in narcotic use (p < 0.001) and higher utilization of acetaminophen (p < 0.001) and ketorolac (p < 0.001) was observed in the ERAS group. Additionally, median time to oral intake, a proxy for postoperative nausea and vomiting [2:00 h (1:15, 2:30) vs. 3:22 h (2:03, 6:15), p < 0.001] and hospital length of stay (LOS) [1.25 days (1.14, 1.34) vs. 2.16 days (1.48, 2.42), p < 0.001] were shorter in the ERAS group. Eleven subjects (10%; ERAS = 5, non-ERAS = 6) experienced post-discharge dehydration, prompting readmission 8 times for 7 (6%) individuals.ConclusionUtilization of ERAS led to a significant decrease narcotic utilization, time to first oral intake, and hospital LOS with no change in adverse events following pediatric metabolic and bariatric surgery. Larger studies, including comparative analysis of health care utilization, should be carried out.Level of evidenceIII.Type of studyTreatment Study.     

Clinical impact of adjuvant radiation therapy delay after neoadjuvant chemotherapy in locally advanced breast cancer

Backgroundand Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown.Material and methodsWe retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8–16 weeks and >16 weeks.ResultsA total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8–16 weeks: HR 0.33; 95% CI 0.13–0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15–0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8–16 weeks: HR 0.22; 95% CI 0.05–0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07–1.15; p = 0.08).ConclusionPORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions.     

Screen detection is a survival predictor independent of pathological grade in colorectal cancer. A prospective cohort study

IntroductionPatients with screened detected colorectal cancer (CRC) have a better survival than patients referred with symptoms. This may be because of cancers being identified in a younger population and at an earlier stage. In this study, we assess whether screened detected CRC has an improved outcome after controlling for key pathological and patient factors known to influence prognosis.MethodThis is a cohort study of all CRC patients diagnosed in NHS Grampian. Patients aged 51–75 years old between June 2007 and July 2017 were included. Data were obtained from a prospectively maintained regional pathology database and outcomes from ISD records. All-cause mortality rates at 1 and 5 years were examined. A Cox proportional hazards regression model was used to estimate the effect of screening status, age, gender, Duke stage, tumour location, extramural venous invasion (EMVI) status and lymph node ratio (LNR) on overall survival.ResultsOf 1618 CRC cases, 449 (27.8%) were screened and 1169 (72.2%) were symptomatic. Screened CRC patients had improved survival compared to non-screened CRC at 1 year (88.9% vs 83.9% p < 0.001) and 5-years (42.5% vs 36.2%; p < 0.001). On multivariable analysis of patients who had no neoadjuvant therapy (n = 1272), screening had better survival (HR 0.57; 95% CI 0.44–0.74; p < 0.001). EMVI (HR 2.22; CI 1.76 to 2.79; p < 0.001) and tumour location were found to affect outcome.ConclusionPatients referred through screening had improved survival compared with symptomatic patients. Further research could be targeted to determine if screened CRC cases are pathologically different to symptomatic cancers or if the screening cohort is inherently more healthy.     

Analgesic efficacy of PECS and serratus plane blocks after breast surgery: A systematic review,meta-analysis and trial sequential analysis

Study objectiveTo determine whether pectoral nerves (PECS) blocks provide effective postoperative analgesia when compared with no regional technique in patients undergoing breast surgery.DesignSystematic review, meta-analysis and trial sequential analysis.SettingOperating room, postoperative recovery area and ward, up to 24 postoperative hours.PatientsPatients undergoing breast surgery under general anaesthesia with either PECS block or no regional technique.InterventionsWe searched five electronic databases for randomized controlled trials comparing PECS block with no block or sham injection.MeasurementsThe primary outcome was rest pain scores (analogue scale, 0–10) at 2 h, analysed according to surgery (mastectomy vs other breast surgery) and regional technique (PECS 2 vs other blocks), among others. Secondary outcomes included morphine equivalent consumption, and rate of postoperative nausea and vomiting at 24 h.Main resultsSixteen trials including 1026 patients were identified. Rest pain scores at 2 h were decreased in the PECS blocks group, with a mean (95%CI) difference of −1.5 (−2.0, −1.0); I2 = 93%; p < 0.001, with no differences between surgery (mastectomy, mean difference [95%CI]: −1.8 [−2.4, −1.2], I² = 91%, p < 0.001; other breast surgery, mean difference [95%CI]: −1.1 [−2.1, −0.1], I² = 94%, p = 0.03; p for subgroup difference = 0.25), and regional technique (PECS 2, mean differences [95%CI]: −1.6 [−2.3, −1.0], I² = 94%, p < 0.001; other blocks, mean differences [95%CI]: −1.3 [−2.4, −0.1], I² = 74%, p = 0.04; p for subgroup difference = 0.57). The rate of postoperative nausea and vomiting was reduced from 30.8% (95%CI: 25.7%, 36.3%) to 18.7% (95%CI, 14.4%, 23.5%; p = 0.01). Similarly, secondary outcomes were significantly improved in the PECS blocks group. The overall quality of evidence was moderate-to-high.ConclusionsThere is moderate-to-high level evidence that PECS blocks provide postoperative analgesia after breast surgery when compared with no regional technique and reduce rate of PONV. This might provide the most benefit to those at high-risk of postoperative pain.