Background:
Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the ...most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations.
Methods:
Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council.
Results:
This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included.
Summary:
The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline.
Hunger, driven by negative energy balance, elicits the search for and consumption of food. While this response is in part mediated by neurons in the hypothalamus, the role of specific cell types in ...other brain regions is less well defined. Here, we show that neurons in the dorsal raphe nucleus, expressing vesicular transporters for GABA or glutamate (hereafter, DRNVgat and DRNVGLUT3 neurons), are reciprocally activated by changes in energy balance and that modulating their activity has opposite effects on feeding—DRNVgat neurons increase, whereas DRNVGLUT3 neurons suppress, food intake. Furthermore, modulation of these neurons in obese (ob/ob) mice suppresses food intake and body weight and normalizes locomotor activity. Finally, using molecular profiling, we identify druggable targets in these neurons and show that local infusion of agonists for specific receptors on these neurons has potent effects on feeding. These data establish the DRN as an important node controlling energy balance.
Display omitted
Display omitted
•Fasting activates DRNVgat neurons; re-feeding activates DRNVGLUT3 neurons•Activation of DRNVgat neurons increases and DRNVGLUT3 suppresses feeding•Inhibiting DRNVgat neurons in obese mice reduces food intake and body weight•DRN neurons can be regulated pharmacologically to drive changes in food intake
A combination of brain mapping and molecular pharmacology approaches identifies specific neurons in the dorsal raphe nucleus as being important regulators of feeding behavior.
The Surgical Infection Society (SIS) Guidelines for the treatment of complicated skin and soft tissue infections (SSTIs) were published in October 2009 in
The purpose of this project was to provide a ...succinct update on the earlier guidelines based on an additional decade of data.
We reviewed the previous guidelines eliminating bite wounds and diabetic foot infections including their associated references. Relevant articles on the topic of complicated SSTIs from 2008-2020 were reviewed and graded individually. Comparisons were then made between the old and the new graded recommendations with review of the older references by two authors when there was disparity between the grades.
The majority of new studies addressed antimicrobial options and duration of therapy particularly in complicated abscesses. There were fewer updated studies on diagnosis and specific operative interventions. Many of the topics addressed in the original guidelines had no new literature to evaluate.
Most recommendations remain unchanged from the original guidelines with the exception of increased support for adjuvant antimicrobial therapy after drainage of complex abscess and increased data for the use of alternative antimicrobial agents.
Necrotizing fasciitis is a major health problem throughout the world. The purpose of this review is to assist providers with the care of these patients through a better understanding of the ...pathophysiology and management options.
This is a collaborative review of the literature between members of the Surgical Infection Society of North America and World Society of Emergency Surgery.
Necrotizing fasciitis continues to be difficult to manage with the mainstay being early diagnosis and surgical intervention. Recognition of at-risk populations assists with the initiation of treatment, thereby impacting outcomes.
Although there are some additional treatment strategies available, surgical debridement and antimicrobial therapy are central to the successful eradication of the disease process.
Discoveries regarding the basic mechanisms underlying malignant disease, rheumatologic disorders, and autoimmune diseases have led to the development of many new therapeutic modalities that target ...components of the immune system. Most of these are antibodies or fusion proteins that interfere with components of the immune response that are playing both pathological and protective roles, resulting in variable degrees of immune suppression and a higher risk of infectious complications.
Review of the English-language literature.
As these modalities are often used in combination with more traditional methods of immune suppression (e.g., corticosteroids), an increasing spectrum of infection is being encountered by clinicians. Febrile neutropenia requires rapid assessment and initiation of empiric broad-spectrum antimicrobial therapy. Persistence despite this therapy should prompt further investigation for drug-resistant bacteria and invasive fungal disease. Important pathogens to consider in patients with neutropenia, chronic steroid exposure, or underlying gastrointestinal malignant diseases include fungi (Candida, Aspergillus) and atypical bacteria (Nocardia, Clostridium septicum).
This review focuses on observations regarding the greater risk of infections associated with many of these new biological modalities, as well as some specific infectious complications that may be encountered more commonly by the surgical consultant.
Despite current antimicrobial stewardship programs (ASPs) being advocated by infectious disease specialists and discussed by national and international policy makers, ASPs coverage remains limited to ...only certain hospitals as well as specific service lines within hospitals. The ASPs incorporate a variety of strategies to optimize antimicrobial agent use in the hospital, yet the exact set of interventions essential to ASP success remains unknown. Promotion of ASPs across clinical practice is crucial to their success to ensure standardization of antimicrobial agent use within an institution. To effectively accomplish this standardization, providers who actively engage in antimicrobial agent prescribing should participate in the establishment and support of these programs. Hence, surgeons need to play a major role in these collaborations. Surgeons must be aware that judicious antibiotic utilization is an integral part of any stewardship program and necessary to maximize clinical cure and minimize emergence of antimicrobial resistance. The battle against antibiotic resistance should be fought by all healthcare professionals. If surgeons around the world participate in this global fight and demonstrate awareness of the major problem of antimicrobial resistance, they will be pivotal leaders. If surgeons fail to actively engage and use antibiotics judiciously, they will find themselves deprived of the autonomy to treat their patients.
Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration ...of the 14 Å internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive form of ovarian cancer. SCCOHT tumors have inactivating mutations in
(BRG1), one of the two mutually exclusive ...ATPases of the SWI/SNF chromatin remodeling complex. To address the role that BRG1 loss plays in SCCOHT tumorigenesis, we performed integrative multi-omic analyses in SCCOHT cell lines +/- BRG1 reexpression. BRG1 reexpression induced a gene and protein signature similar to an epithelial cell and gained chromatin accessibility sites correlated with other epithelial originating TCGA tumors. Gained chromatin accessibility and BRG1 recruited sites were strongly enriched for transcription-factor-binding motifs of AP-1 family members. Furthermore, AP-1 motifs were enriched at the promoters of highly upregulated epithelial genes. Using a dominant-negative AP-1 cell line, we found that both AP-1 DNA-binding activity and BRG1 reexpression are necessary for the gene and protein expression of epithelial genes. Our study demonstrates that BRG1 reexpression drives an epithelial-like gene and protein signature in SCCOHT cells that depends upon by AP-1 activity.
infection (CDI) can result in life-threatening illness requiring surgery. Surgical options for managing severe or fulminant, non-perforated
colitis include total abdominal colectomy with end ...ileostomy or creation of a diverting loop ileostomy with antegrade vancomycin lavage.
The Surgical Infection Society's Therapeutics and Guidelines Committee convened to develop guidelines for summarizing the current SIS recommendations for total abdominal colectomy versus diverting loop ileostomy with antegrade lavage for severe or fulminant, non-perforated
colitis. PubMed, Embase, and the Cochrane database were searched for pertinent studies. Severe infection was defined as laboratory diagnosis of
infection with leukocytosis (white blood cell count of ≥15,000 cells/mL) or elevated creatinine (serum creatinine level >1.5 mg/dL). Fulminant infection was defined as laboratory diagnosis of
infection with hypotension or shock, ileus, or megacolon. Perforation was defined as complete disruption of the colon wall. Total abdominal colectomy was defined as resection of the ascending, transverse, descending, and sigmoid colon with end ileostomy. For the purpose of the guideline, the terms subtotal colectomy, total abdominal colectomy, and rectal-sparing total colectomy were used interchangeably. Diverting loop ileostomy with antegrade enema was defined as creation of both a diverting loop ileostomy with intra-operative colonic lavage and post-operative antegrade vancomycin unless otherwise specified. Evaluation of the published evidence was performed using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation.
We recommend that total abdominal colectomy be the procedure of choice for definitive therapy of severe or fulminant, non-perforated
colitis. In select patients, colon preservation using diverting loop ileostomy with intra-colonic vancomycin may be associated with higher rates of ostomy reversal and restoration of gastrointestinal continuity but may lead to development of recurrent
colitis.
This guideline summarizes the current Surgical Infection Society recommendations regarding use of total abdominal colectomy versus diverting loop ileostomy with antegrade lavage for adults with severe or fulminant, non-perforated
infection.
Many rare ovarian cancer subtypes, such as small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), have poor prognosis due to their aggressive nature and resistance to standard platinum- and ...taxane-based chemotherapy. The development of effective therapeutics has been hindered by the rarity of such tumors. We sought to identify targetable vulnerabilities in rare ovarian cancer subtypes.
We compared the global proteomic landscape of six cases each of endometrioid ovarian cancer (ENOC), clear cell ovarian cancer (CCOC), and SCCOHT to the most common subtype, high-grade serous ovarian cancer (HGSC), to identify potential therapeutic targets. IHC of tissue microarrays was used as validation of arginosuccinate synthase (ASS1) deficiency. The efficacy of arginine-depriving therapeutic ADI-PEG20 was assessed
using cell lines and patient-derived xenograft mouse models representing SCCOHT.
Global proteomic analysis identified low ASS1 expression in ENOC, CCOC, and SCCOHT compared with HGSC. Low ASS1 levels were validated through IHC in large patient cohorts. The lowest levels of ASS1 were observed in SCCOHT, where ASS1 was absent in 12 of 31 cases, and expressed in less than 5% of the tumor cells in 9 of 31 cases. ASS1-deficient ovarian cancer cells were sensitive to ADI-PEG20 treatment regardless of subtype
. Furthermore, in two cell line mouse xenograft models and one patient-derived mouse xenograft model of SCCOHT, once-a-week treatment with ADI-PEG20 (30 mg/kg and 15 mg/kg) inhibited tumor growth
.
Preclinical
and
studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT.
PDF
