Nonoperative Treatment of Diverticulitis and Appendicitis: Which Antibiotic Regimen Fails?

INTRODUCTION: Diverticulitis and appendicitis are common emergency general surgical conditions. Both can be treated with antibiotics alone; however, no antibiotic regimen has been identified as superior to others. In this study, we review different antibiotic regimens and their rates of failure. METHODS: Retrospective cohort study of patients treated empirically with antibiotics for diverticulitis or appendicitis from January 1, 2018, to December 31, 2020, at an independent academic hospital in the Midwest. RESULTS: A total of 587 (appendicitis, n = 43; diverticulitis, n = 544) patients were included in the cohort. They were equally male (49%) and female (51%) with a median age of 59 y. Three major antibiotic classes were compared: cephalosporin + metronidazole (C + M), penicillins, and quinolone + metronidazole. Appendicitis patients were more likely to receive C + M for empiric treatment (73%, P < 0.001), while diverticulitis patients were more likely to receive quinolone + metronidazole (45%, P < 0.001). Patients empirically treated with antibiotics for appendicitis were more likely than those treated for diverticulitis to require additional antibiotics or procedure within 90 d (33% versus 13%, respectively; P = 0.005). Empiric treatment with C + M for diverticulitis was more likely to be associated with the need for additional antibiotics or procedures within 90 d than treatment with other regimens (P = 0.003). Choice of antibiotic for empiric treatment did not correlate with death at 90 d for appendicitis or diverticulitis. Diverticulitis patients who were initially treated as inpatients and were prescribed C + M at hospital discharge had a higher rate of death than those who were prescribed the other antibiotics (P = 0.04). CONCLUSIONS: Empiric antibiotic treatment of appendicitis is more likely to be associated with additional antibiotics or procedure when compared with diverticulitis; however, antibiotic choice did not correlate with any of the other outcomes. Empiric treatment with a C + M for diverticulitis was more likely to be correlated with the need for additional antibiotics or procedure within 90 d.

MicroRNA Expression Profiling of Cutaneous Squamous Cell Carcinomas Arising in Different Sites.

OBJECTIVE: To examine the microRNA (miRNA) expression profile of cutaneous squamous cell carcinoma (cSCC) tumors from aggressive head and neck locations compared with nonaggressive anatomic sites and normal controls. STUDY DESIGN: Retrospective analysis of miRNA expression. SETTING: Tertiary care center. SUBJECTS AND METHODS: Tissue samples were collected from 3 anatomic regions: aggressive head and neck sites (ie, ears/lip), nonaggressive locations (ie, extremities/trunk), and adjacent normal skin. RNA was isolated from tissue cores of 45 samples (18 aggressive sites, 15 nonaggressive sites, and 12 normal-adjacent skin). miRNA expression analysis was completed for approximately 800 miRNAs using the NanoString nCounter panel. Five candidate miRNAs were selected for validation. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed on the original samples plus 30 additional tissue samples (7 aggressive sites, 14 nonaggressive sites, and 9 normal-adjacent skin). RESULTS: Five candidate miRNAs with significant differences in miRNA expression (P < 0 ≤ .001) from discovery samples were selected: miR-21, miR-31, let-7g, miR-93, and miR-22. Relative expression for these miRNAs using qRT-PCR in the new sample set did not reveal any significant differences using 1-way analysis of variance. When sets were combined, miR-21 showed increased expression in aggressive tumors relative to nonaggressive tumors (P = .009), but no others reached statistical significance. CONCLUSION: cSCC behaves more aggressively when originating from specific anatomical subsites of the head and neck. Of 5 miRNAs evaluated, only miR-21 showed significantly higher expression in tumors from aggressive sites relative to nonaggressive sites. Larger sample sizes are needed to evaluate other miRNAs.

Does Timing of Inferior Vena Cava Filter Retrieval Planning Impact Retrieval Rates? A Comparison of Planning Before or After Hospital Discharge.

INTRODUCTION: Indwelling inferior vena cava (IVC) filters are associated with complications, and the US Food and Drug Administration recommends their prompt removal when no longer indicated. Therefore, assessing strategies for increasing retrieval rates is warranted. OBJECTIVE: To analyze the variability of IVC filter retrieval rates within our institution based on 2 separate, pre-existing processes in which IVC retrieval is planned for before or after hospital discharge. METHODS: Retrospective chart review was completed for all IVC filters placed in adults between January 2005 and March 2015. Demographics and clinical data related to filter placement and retrieval were abstracted. Patients were classified into 2 groups: patients who had a trauma consultation trauma and nontrauma medical and surgical patients medical. The trauma group patients were subject to a 2-layer tracking process, in which retrieval planning was done before discharge, versus the medical group with a single-layer tracking process and retrieval planning done after discharge. RESULTS: Of the 588 filter placements analyzed, 236 were placed in trauma patients and 352 were placed for medical reasons. The retrieval rate of the entire cohort was 45% (262/588), with the rate among trauma patients more than double that of medical patients (155/236, 66% and 107/352, 30%; respectively, P < 0.0001). CONCLUSION: IVC filter retrieval rate was increased when filter removal was included in discharge planning versus postdischarge tracking. A systematic, multidisciplinary strategic approach to IVC filter management has great potential to improve filter utilization, resource allocation, patient safety, and filter retrieval.

Unique CD8+ T Cell-Mediated Immune Responses Primed in the Liver.

BACKGROUND: The liver immune environment is tightly regulated to balance immune activation with immune tolerance. Understanding the dominant immune pathways initiated in the liver is important because the liver is a site for cell transplantation, such as for islet and hepatocyte transplantation. The purpose of this study is to examine the consequences of alloimmune stimulation when allogeneic cells are transplanted to the liver in comparison to a different immune locale, such as the kidney. METHODS: We investigated cellular and humoral immune responses when allogeneic hepatocytes are transplanted directly to the recipient liver by intraportal injection. A heterotopic kidney engraftment site was used for comparison to immune activation in the liver microenvironment. RESULTS: Transplantation of allogeneic hepatocytes delivered directly to the liver, via recipient portal circulation, stimulated long-term, high magnitude CD8 T cell-mediated allocytotoxicity. CD8 T cells initiated significant in vivo allocytotoxicity as well as rapid rejection of hepatocytes transplanted to the liver even in the absence of secondary lymph nodes or CD4 T cells. In contrast, in the absence of recipient peripheral lymphoid tissue and CD4 T cells, CD8-mediated in vivo allocytotoxicity was abrogated, and rejection was delayed when hepatocellular allografts were transplanted to the kidney subcapsular site. CONCLUSIONS: These results highlight the CD8-dominant proinflammatory immune responses unique to the liver microenvironment. Allogeneic cells transplanted directly to the liver do not enjoy immune privilege but rather require immunosuppression to prevent rejection by a robust and persistent CD8-dependent allocytotoxicity primed in the liver.

Increasing Follow-up Outcomes of At-Risk Alcohol Patients Using Motivational Interviewing.

Our trauma division implemented a screening, brief intervention, and referral to treatment (SBIRT) program in 2009 and has maintained more than 92% screening rate for all inpatient admissions since inception. Brief interventions are proven to be more likely to effect and reinforce change if a follow-up contact is made with patients. This led to discussion regarding whether identified patients were more likely to follow up with our SBIRT wellness specialist using motivational interviewing or with our partners, exercise physiology, who use traditional interviewing techniques. We retrospectively reviewed more than 3,000 inpatient admissions in which screening for at-risk alcohol use were positive. Fifty-one percent of identified patients were referred for wellness specialist consultation with a follow-up rate of 52% compared with a follow-up rate of only 21% in the exercise physiology group. Motivational interviewing is more effective in encouraging at-risk alcohol users to participate in follow-up care.

Inhibition of recall responses through complementary therapies targeting CD8+ T-cell- and alloantibody-dependent allocytotoxicity in sensitized transplant recipients.

Allospecific T memory cell responses in transplant recipients arise from environmental exposure to previous transplantation or cross-reactive heterologous immunity. Unfortunately, these memory responses pose a significant barrier to the survival of transplanted tissue. We have previously reported that concurrent inhibition of CD154 and LFA-1 suppresses primary CD8-dependent rejection responses that are not controlled by conventional immunosuppressive strategies. We hypothesized that CD154- and LFA-1-mediated inhibition, by targeting activation as well as effector functions, may also be efficacious for the control of alloreactive CD8+ T-cell responses in sensitized hosts. We found that treatment with anti-LFA-1 mAb alone enhanced transplant survival and reduced CD8-mediated cytotoxicity in sensitized CD4 KO recipients. However, treatment with anti-CD154 mAb alone did not have an effect. Notably, when both CD4- and CD8-dependent rejection pathways are operative (wild-type sensitized recipients), LFA-1 significantly inhibited CD8-mediated in vivo allocytotoxicity but did not correspond with enhanced hepatocyte survival. We hypothesized that this was due to alloantibody-mediated rejection. When anti-LFA-1 mAb treatment was combined with macrophage depletion, which we have previously reported impairs alloantibody-mediated parenchymal cell damage, in vivo cytotoxic effector function was significantly decreased and was accompanied by significant enhancement of hepatocyte survival in sensitized wild-type recipients. Therefore, LFA-1 is a potent therapeutic target for reduction of CD8-mediated cytotoxicity in sensitized transplant recipients and can be combined with other treatments that target non-CD8-mediated recall alloimmunity.

Cytotoxic effector function of CD4-independent, CD8(+) T cells is mediated by TNF-α/TNFR.

BACKGROUND: Liver parenchymal cell allografts initiate both CD4-dependent and CD4-independent, CD8(+) T cell-mediated acute rejection pathways. The magnitude of allospecific CD8(+) T cell in vivo cytotoxic effector function is maximal when primed in the presence of CD4(+) T cells. The current studies were conducted to determine if and how CD4(+) T cells might influence cytotoxic effector mechanisms. METHODS: Mice were transplanted with allogeneic hepatocytes. In vivo cytotoxicity assays and various gene-deficient recipient mice and target cells were used to determine the development of Fas-, TNF-α-, and perforin-dependent cytotoxic effector mechanisms after transplantation. RESULTS: CD8(+) T cells maturing in CD4-sufficient hepatocyte recipients develop multiple (Fas-, TNF-α-, and perforin-mediated) cytotoxic mechanisms. However, CD8(+) T cells, maturing in the absence of CD4(+) T cells, mediate cytotoxicity and transplant rejection that is exclusively TNF-α/TNFR-dependent. To determine the kinetics of CD4-mediated help, CD4(+) T cells were adoptively transferred into CD4-deficient mice at various times posttransplant. The maximal influence of CD4(+) T cells on the magnitude of CD8-mediated in vivo allocytotoxicityf occurs within 48 hours. CONCLUSION: The implication of these studies is that interference of CD4(+) T cell function by disease or immunotherapy will have downstream consequences on both the magnitude of allocytotoxicity as well as the cytotoxic effector mechanisms used by allospecific CD8(+) cytolytic T cells.

Evolving management of pancreatic injury.

PURPOSE OF REVIEW: In this study we present a concise review of the evolving management of traumatic injury to the pancreas, including diagnostic approaches and options for operative and nonoperative intervention. RECENT FINDINGS: New diagnostic adjuncts can be used for the evaluation of injury to the pancreas and pancreatic duct. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) are used as diagnostic modalities for duct evaluation. ERCP can be therapeutic with sphincterotomy and/or stenting for duct disruption. Computed tomography scan is the initial imaging study of choice for pancreatic injury, but is also used for drainage of pancreatic abscesses or pseudocysts. SUMMARY: Nonoperative management of solid organ injuries is the recommended treatment in hemodynamically stable patients. This strategy is now being successfully applied to pancreatic injuries in specific situations. However, the mainstays of pancreatic injury remain the same. The identification of pancreatic duct injury is the top priority. Management includes distal resection, debridement, and closed suction drainage of pancreatic injuries.

Critical role of effector macrophages in mediating CD4-dependent alloimmune injury of transplanted liver parenchymal cells.

Despite the recognition that humoral rejection is an important cause of allograft injury, the mechanism of Ab-mediated injury to allograft parenchyma is not well understood. We used a well-characterized murine hepatocellular allograft model to determine the mechanism of Ab-mediated destruction of transplanted liver parenchymal cells. In this model, allogeneic hepatocytes are transplanted into CD8-deficient hosts to focus on CD4-dependent, alloantibody-mediated rejection. Host serum alloantibody levels correlated with in vivo allospecific cytotoxic activity in CD8 knockout hepatocyte rejector mice. Host macrophage depletion, but not CD4(+) T cell, NK cell, neutrophil, or complement depletion, inhibited in vivo allocytotoxicity. Recipient macrophage deficiency delayed CD4-dependent hepatocyte rejection and inhibited in vivo allocytotoxicity without influencing alloantibody production. Furthermore, hepatocyte coincubation with alloantibody and macrophages resulted in Ab-dependent hepatocellular cytotoxicity in vitro. These studies are consistent with a paradigm of acute humoral rejection in which CD4(+) T cell-dependent alloantibody production results in the targeting of transplanted allogeneic parenchymal cells for macrophage-mediated cytotoxic immune damage. Consequently, strategies to eliminate recipient macrophages during CD4-dependent rejection pathway may prolong allograft survival.