WSES/GAIS/WSIS/SIS-E/AAST global clinical pathways for patients with skin and soft tissue infections

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections.Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs.An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.

Models for Assessing Strategies for Improving Hospital Capacity for Handling Patients during a Pandemic

Objective: The aim of this study was to investigate the performance of key hospital units associated with emergency care of both routine emergency and pandemic (COVID-19) patients under capacity enhancing strategies. Methods: This investigation was conducted using whole-hospital, resource-constrained, patient-based, stochastic, discrete-event simulation models of a generic 200-bed urban U.S. tertiary hospital serving routine emergency and COVID-19 patients. Systematically designed numerical experiments were conducted to provide generalizable insights into how hospital functionality may be affected by the care of COVID-19 pandemic patients along specially designated care paths under changing pandemic situations from getting ready to turning all of its resources to pandemic care. Results: Several insights are presented. For example, each day of reduction in average ICU length of stay increases intensive care unit patient throughput by up to 24% for high COVID-19 daily patient arrival levels. The potential of five specific interventions and two critical shifts in care strategies to significantly increase hospital capacity is described. Conclusions: These estimates enable hospitals to repurpose space, modify operations, implement crisis standards of care, prepare to collaborate with other health care facilities, or request external support, increasing the likelihood that arriving patients will find an open staffed bed when one is needed.

Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations

Lung cancer has traditionally been classified by histology. However, a greater understanding of disease biology and the identification of oncogenic driver alterations has dramatically altered the therapeutic landscape. Consequently, the new classification paradigm of non–small-cell lung cancer is further characterized by molecularly defined subsets actionable with targeted therapies and the treatment landscape is becoming increasingly complex. This review encompasses the current standards of care for targeted therapies in lung cancer with driver molecular alterations. Targeted therapies for EGFR exon 19 deletion and L858R mutations, and ALK and ROS1 rearrangements are well established. However, there is an expanding list of approved targeted therapies including for BRAF V600E, EGFR exon 20 insertion, and KRAS G12C mutations, MET exon 14 alterations, and NTRK and RET rearrangements. In addition, there are numerous other oncogenic drivers, such as HER2 exon 20 insertion mutations, for which there are emerging efficacy data for targeted therapies. The importance of diagnostic molecular testing, intracranial efficacy of novel therapies, the optimal sequencing of therapies, role for targeted therapies in early-stage disease, and future directions for precision oncology approaches to understand tumor evolution and therapeutic resistance are also discussed.

The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma

Background Melanoma-intrinsic activated β-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS). Methods We examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database. We assessed APC/CTNNB1 mutations as predictors of response to immunotherapies in a clinicopathologically annotated metastatic patient cohort from three US melanoma centers. Results In the TCGA-SKCM patient cohort (n = 434) presence of a somatic APC/CTNNB1 mutation was associated with a worse outcome only in stage IV melanoma (n = 82, median OS of APC/CTNNB1 mutants vs. wild-type was 8.15 vs. 22.8 months; log-rank hazard ratio 4.20, p = 0.011). APC/CTNNB1 mutation did not significantly affect lymphocyte distribution and density. In the 3-melanoma institution cohort, tumor tissues underwent targeted panel sequencing using two standards of care assays. We identified 55 patients with stage IV melanoma and APC/CTNNB1 genetic aberrations (mut) and 169 patients without (wt). At a median follow-up of more than 25 months for both groups, mut compared with wt patients had slightly more frequent (44% vs. 39%) and earlier (66% vs. 45% within six months from original diagnosis of stage IV melanoma) development of brain metastases. Nevertheless, time-to-development of brain metastases was not significantly different between the two groups. Fortunately, mut patients had similar clinical benefits from PD-1 inhibitor-based treatments compared to wt patients (median OS 26.1 months vs. 29.9 months, respectively, log-rank p = 0.23). Less frequent mutations in the NF1, RAC1, and PTEN genes were seen in the mut compared with wt patients from the 3-melanoma institution cohort. Analysis of brain melanoma tumor tissues from a separate craniotomy patient cohort (n = 55) showed that melanoma-specific, activated β-catenin (i.e., nuclear localization) was infrequent (n = 3, 6%) and not prognostic in established brain metastases. Conclusions APC/CTNNB1 mutations are associated with a worse outcome in stage IV melanoma and early brain metastases independent of tumor-infiltrating lymphocyte density. However, PD1 inhibitor-based treatments provide comparable benefits to both mut and wt patients with stage IV melanoma.

Ethical analysis examining the prioritisation of living donor transplantation in times of healthcare rationing

The transplant community has faced unprecedented challenges balancing risks of performing living donor transplants during the COVID-19 pandemic with harms of temporarily suspending these procedures. Decisions regarding postponement of living donation stem from its designation as an elective procedure, this despite that the Centers for Medicare and Medicaid Services categorise transplant procedures as tier 3b (high medical urgency—do not postpone). In times of severe resource constraints, health systems may be operating under crisis or contingency standards of care. In this manuscript, the United Network for Organ Sharing Ethics Workgroup explores prioritisation of living donation where health systems operate under contingency standards of care and provide a framework with recommendations to the transplant community on how to approach living donation in these circumstances.To guide the transplant community in future decisions, this analysis suggests that: (1) living donor transplants represent an important option for individuals with end-stage liver and kidney disease and should not be suspended uniformly under contingency standards, (2) exposure risk to SARS-CoV-2 should be balanced with other risks, such as exposure risks at dialysis centres. Because many of these risks are not quantifiable, donors and recipients should be included in discussions on what constitutes acceptable risk, (3) transplant hospitals should strive to maintain a critical transplant workforce and avoid diverting expertise, which could negatively impact patient preparedness for transplant, (4) transplant hospitals should consider implementing protocols to ensure early detection of SARS-CoV-2 infections and discuss these measures with donors and recipients in a process of shared decision-making.

Metastatic gastroesophageal cancer in older patients – is this patient cohort represented in clinical trials?

Background Older patients are underrepresented in the clinical trials that determine the standards of care for oncological treatment. We conducted a review to identify whether there have been age-restrictive inclusion criteria in clinical trials over the last twenty five years, focusing on patients with metastatic gastroesophageal cancer. Methods A search strategy was developed encompassing Embase, PubMed and The Cochrane Library databases. Completed phase III randomised controlled trials evaluating systemic anti-cancer therapies in metastatic gastroesophageal malignancies from 1st January 1995 to 18th November 2020 were identified. These were screened for eligibility using reference management software (Covidence; Veritas Health Innovation Ltd). Data including age inclusion/exclusion criteria and median age of participants were recorded. The percentage of patients ≥ 65 enrolled was collected where available. The change over time in the proportion of studies using an upper age exclusion was estimated using a linear probability model. Results Three hundred sixty-three phase III studies were identified and screened, with 66 trials remaining for final analysis. The majority of trials were Asian (48%; n = 32) and predominantly evaluated gastric malignancies, (86%; n = 56). The median age of participants was 62 (range 18–94). Thirty-two percent (n = 21) of studies specified an upper age limit for inclusion and over half of these were Asian studies. The median age of exclusion was 75 (range 65–80). All studies prior to 2003 used an upper age exclusion (n = 12); whereas only 9 that started in 2003 or later did (17%). Among later studies, there was a very modest downward yearly-trend in the proportion of studies using an upper age exclusion (-0.02 per year; 95%CI -0.05 to 0.01; p = 0.31). Fifty-two percent (n = 34) of studies specified the proportion of their study population who were ≥ 65 years. Older patients represented only 36% of the trial populations in these studies (range 7–60%). Conclusions Recent years have seen improvements in clinical trial protocols, with many no longer specifying restrictive age criteria. Reasons for poor representation of older patients are complex and ongoing efforts are needed to broaden eligibility criteria and prioritise the inclusion of older adults in clinical trials.

Investigation of the possible effectiveness of osteopathic correction in the complex treatment of children in the first year of life with hip dysplasia

Introduction. Congenital dysplasia of the hip joints is one of the main among congenital diseases of the musculoskeletal system in children and requires a long period of treatment, including in a hospital settings. Standard methods of treatment contain the orthopedic and rehabilitation measures: the use of abduction splints, a complex of physiotherapy exercises, general massage, the use of various physiotherapeutic procedures. Osteopathic correction is not included in the standards of care for this category of patients. At the same time, these standard treatment methods do not always give a desired result, and sometimes even lead to the development of complications. All this facts determines the need to search for additional therapeutic techniques.The aim of the study is to research the possible effectiveness of osteopathic correction as part of the complex treatment of children in the first year of life with hip dysplasia.Materials and methods. The study included 34 children with a diagnosis of hip dysplasia (ICD code-10 — Q65.8). The patients were randomly divided into 2 equivalent groups: study and control. Participants in both groups received standard treatment; the participants of the main group additionally underwent osteopathic correction of the revealed somatic dysfunctions. Before and after the course of treatment, the patients' osteopathic status, the disease clinical manifestations, and the X-ray data of the hip joints were assessed.Results. The inclusion of osteopathic correction in the complex with standard treatment procedures for children of the first year of life with hip dysplasia is accompanied by a statistically significant decrease in the detection frequency of the somatic dysfunctions at the regional and local levels. The median duration of standard orthopedic treatment also decreases (p<0,05).Conclusion. The obtained results demonstrate that the inclusion of osteopathic correction in the complex treatment of children in the first year of life with hip dysplasia shortens the treatment time for patients. It is recommended to continue research in this direction with a larger sample size.

Improving medical standards of care to children of an early and preschool age with urinary tract infections at the primary care stage

Timely diagnosis, prognostic value of clinical signs and further treatment of patients of an early age with urinary tract infections (UTI) during outpatient stage are important constituents of an integrated management of patients in childhood. The article deals with new approaches concerning clinical algorithm in diagnosis of urinary tract infections in children. The algorithm of diagnostic and therapeutic measures for providing care to children under 5 years of age with urinary tract infections, in particular at the stage of primary care, includes: diagnosis of urinary tract infection in young children using The Diagnosis of Urinary Tract infection in Young children, patient’s examination by Gorelick Scale and UTIcalc, imaging methods with mandatory ultrasound of the kidneys and bladder, micturating cystogram after the first episode of infection in boys and the second — in girls, the prescription of antibiotic therapy based on data from regional monitoring of antibiotic resistance of the main groups of uropathogens, monitoring antibiotic resistance using electronic means and the implementation in microbiological laboratories of the guidelines of the European Committee on Antimicrobial Susceptibility Testing, as well as introduction of the prescription sale of antibiotics.