Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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ERBB2 mutation is associated with sustained tumor cell proliferation after short-term preoperative endocrine therapy in early lobular breast cancer

Invasive lobular breast cancer (ILC) is a special breast cancer (BC) subtype and is mostly hormone receptor (HR)-positive and ERBB2 non-amplified. Endocrine therapy restrains tumor proliferation and is the mainstay of lobular BC treatment. Mutation of ERBB2 has been associated with recurrent ILC. However, it is unknown whether ERBB2 mutation impacts on the otherwise exquisite responsiveness of early ILC to endocrine therapy. We have recently profiled n = 622 HR-positive early BCs from the ADAPT trial for mutations in candidate genes involved in endocrine resistance, including ERBB2. All patients were treated with short-term preoperative endocrine therapy (pET, tamoxifen or aromatase inhibitors) before tumor resection. Tumor proliferation after endocrine therapy (post-pET Ki67 index) was determined prospectively by standardized central pathology assessment supported by computer-assisted image analysis. Sustained or suppressed proliferation were defined as post-pET Ki67 =10% or <10%. Here, we report a subgroup analysis pertaining to ILCs in this cohort. ILCs accounted for 179/622 (28.8%) cases. ILCs were enriched in mutations in CDH1 (124/179, 69.3%, P < 0.0001) and ERBB2 (14/179, 7.8%, P < 0.0001), but showed fewer mutations in TP53 (7/179, 3.9%, P = 0.0048) and GATA3 (11/179, 6.1%, P < 0.0001). Considering all BCs irrespective of subtypes, ERBB2 mutation was not associated with proliferation. In ILCs, however, ERBB2 mutations were 3.5-fold more common in cases with sustained post-pET proliferation compared to cases with suppressed post-pET proliferation (10/75, 13.3% versus 4/104, 3.8%, P = 0.0248). Moreover, ERBB2 mutation was associated with high Oncotype DX recurrence scores (P = 0.0087). In summary, our findings support that ERBB2 mutation influences endocrine responsiveness in early lobular BC

Abstract P2-13-03: KEYRICHED-1 - A prospective, multicenter, open label, neoadjuvant phase II single arm study with pembrolizumab in combination with dual anti-HER2 blockade with trastuzumab and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype

Abstract Background: De-escalating strategies seem promising inHER2-positive early breast cancer (EBC) and chemo-free regimens are thus of keyinterest. Recent data have underlined the role of tumor immunogenicity inresponse to de-escalated neoadjuvant anti-HER2 therapy. Therefore, theprospective single arm hypothesis-generating phase II KEYRICHED-1 trial (NCT03988036)investigates the pCR rate in patients with HER2-enriched EBC receiving fourcycles of the dual anti-HER2 blockade in combination with the checkpointinhibitor pembrolizumab. Initial studies with dual antibody-based HER2 blockadealone were able to achieve pCR-rates of 20-40%, which did not quite match the pCRrates obtained with concurrent chemotherapy. KEYRICHED-1 aims at achieving pCR-ratescomparable to standard chemotherapy-containing regimens by incorporating appropriatemolecular selection and immune oncology. Methods: A total of 48 pre- and postmenopausal patients with newly diagnosed HER22+ or 3+ EBC (stage I-III) and HER2-enriched (HER2-E) subtype by PAM50 wereenrolled in this single-arm study. All patients received four cycles of studytreatment with pembrolizumab (200mg), trastuzumab biosimilar (Trazimera®,loading dose 8mg/kg bodyweight (BW), maintenance dose 6mg/kg BW), and pertuzumab(loading dose 840mg/kg BW, maintenance dose 420mg/kg BW) q21d . Primaryendpoint was centrally confirmed pCR (ypT0/is, ypN0). The trial was planned asa Simon's two-Stage design (null and alternative pCR were 40% and 60%); interimanalysis after 16 patients had to show a pCR rate of at least 50% to continuerecruitment. Results: Between 05/2020 and 03/2021, 98 patients werescreened. N=52 (55%) had HER2-E subtype,of whom 48 patients entered thetreatment phase. Median patient age was 57 years (28-83). 65% had tumors &amp;gt; 2cm and 30% positive lymph node status. Centrally confirmed pCR rate in surgicalspecimens was 46% (95% CI 0.31-0.62) in the 43 patients of the per protocolpopulation, and 52% (95%CI 0.37-0.67) in all 46 evaluable patients (localassessment; two pCRs verified only by core biopsy) (p=0.22 and p=0.06 for nullhypothesis, respectively). Despite HER2-E subtype, no pCR was observed in the 4patients with immunohistochemical (IHC) HER2 2+/ISH-positive status in contrastto 20/39 (51.2%) pCRs in IHC HER2 3+ tumors. Centrally confirmed pCR rate in HR+/HER2+tumors was38.5% compared to 58.5% in HR-/HER2+ tumors. No new safety signals wereobserved. Conclusions: These are the first results of a neoadjuvant chemotherapy-free12-week de-escalation anti-HER2-regimen with trastuzumab and pertuzumab incombination with the PD-1 inhibitor pembrolizumab in patients with a HER2-E EBC.In the context of the WSG ADAPT HER2+ de-escalation trials the observed pCRrates compare favourably in HR+ as well as HR- HER2 EBC. Moreover, KEYRICHED-1demonstrates that with appropriate molecular patient selection clinicallymeaningful pCR rates in the range of those obtained with longer, more toxicchemotherapy-containing regimens can be achieved. Citation Format: Sherko Kuemmel, Oleg Gluz, Mattea Reinisch, Athina Kostara, Iris Scheffen, Monika Graeser, Kerstin Luedtke-Heckenkamp, Andreas Hartkopf, Felix Hilpert, Angela Kentsch, Carsten Ziske, Reinhard Depenbusch, Michael Braun, Jens Blohmer, Christine zu Eulenburg, Matthias Christgen, Stephan Bartels, Hans Kreipe, Enrico Pelz, Peter Schmid, Nadia Harbeck. KEYRICHED-1 - A prospective, multicenter, open label, neoadjuvant phase II single arm study with pembrolizumab in combination with dual anti-HER2 blockade with trastuzumab and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-03.</jats:p

Abstract PD10-11: Keyriched-1- A prospective, multicenter, open label, neoadjuvant phase ii single arm study with pembrolizumab in combination with dual anti-HER2 blockade with trastuzumab and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype

Abstract Background: De-escalating strategies seem promising in HER2-positive early breast cancer (EBC) and chemo-free regimens are thus of key interest. Recent data have underlined the role of tumor immunogenicity in response to de-escalated neoadjuvant anti-HER2 therapy. Therefore, the prospective single arm hypothesis-generating phase II KEYRICHED-1 trial (NCT03988036) investigates the pCR-rate in patients with HER2-enriched EBC receiving four cycles of the dual anti-HER2 blockade in combination with the checkpoint inhibitor pembrolizumab. Initial studies with dual antibody-based HER2 blockade alone were able to achieve pCR-rates of 20-40%, which did not quite match the pCR-rates obtained with concurrent chemotherapy. KEYRICHED-1 aims at achieving pCR-rates comparable to standard chemotherapy-containing regimens by incorporating appropriate molecular selection and immune oncology.. Methods: A total of 48 pre- and postmenopausal patients with newly diagnosed HER2 2+ or 3+ EBC (stage I-III) and HER2-enriched (HER2-E) subtype by PAM50 were enrolled in this single-arm study. All patients received four cycles of study treatment with pembrolizumab (200mg), trastuzumab biosimilar (Trazimera®, loading dose 8mg/kg bodyweight (BW), maintenance dose 6mg/kg BW), and pertuzumab (loading dose 840mg/kg BW, maintenance dose 420mg/kg BW) q21d. Primary endpoint was centrally confirmed pCR (ypT0/is, ypN0). The trial was planned as a Simon's two-stage design (null and alternative pCR were 40% and 60%); interim analysis after 16 patients had to show a pCR rate of at least 50% to continue recruitment.. Results: Between 05/2020 and 03/2021, 98 patients were screened. N=52 (55%) had HER2-E subtype, of whom 48 patients entered the treatment phase. Median patient age was 57 years (28-83). 65% had tumors &amp;gt; 2 cm and 30% positive lymph node status. Centrally confirmed pCR-rate in surgical specimens was 46% (95% CI 0.31-0.62) in the 43 patients of the per-protocol-population, and 52% (95%CI 0.37-0.67) in all 46 evaluable patients (local assessment; two pCRs verified only by core biopsy) (p=0.22 and p=0.06 for null hypothesis, respectively). Despite HER2-E subtype, no pCR was observed in the four patients with immunohistochemical (IHC) HER2 2+/ISH-positive status in contrast to 20/39 (51.2%) pCR in IHC HER2 3+ tumors. Centrally confirmed pCR-rate in HR+/HER2+ tumors was 38.5% compared to 58.5% in HR-/HER2+ tumors. No new safety signals were observed.. Conclusions: These are the first results of a neoadjuvant chemotherapy-free 12-week de-escalation anti-HER2-regimen with trastuzumab and pertuzumab in combination with the PD-1 inhibitor pembrolizumab in patients with a HER2-E EBC. In the context of the WSG ADAPT HER2+ de-escalation trials the observed pCR-rates compare favorably in HR+ as well as HR- HER2+ EBC. Moreover, KEYRICHED-1 demonstrates that with appropriate molecular patient selection clinically meaningful pCR-rates in the range of those obtained with longer, more toxic chemotherapy-containing regimens can be achieved. Citation Format: Sherko Kuemmel, Oleg Gluz, Mattea Reinisch, Athina Kostara, Iris Scheffen, Monika Graeser, Rachel Wuerstlein, Ulrike Nitz, Kerstin Luedtke-Heckenkamp, Andreas Hartkopf, Felix Hilpert, Angela Kentsch, Carsten Ziske, Reinhard Depenbusch, Michael Braun, Jens Blohmer, Christine zu Eulenburg, Matthias Christgen, Stephan Bartels, Hans Kreipe, Enrico Pelz, Peter Schmid, Nadia Harbeck. Keyriched-1- A prospective, multicenter, open label, neoadjuvant phase ii single arm study with pembrolizumab in combination with dual anti-HER2 blockade with trastuzumab and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD10-11.</jats:p