Multicenter Assessment of Cryoanalgesia Use in Minimally Invasive Repair of Pectus Excavatum: A 20-center Retrospective Cohort Study.

OBJECTIVE: To assess the clinical implications of cryoanalgesia for pain management in children undergoing minimally invasive repair of pectus excavatum (MIRPE). BACKGROUND: MIRPE entails significant pain management challenges, often requiring high postoperative opioid use. Cryoanalgesia, which blocks pain signals by temporarily ablating intercostal nerves, has been recently utilized as an analgesic adjunct. We hypothesized that the use of cryoanalgesia during MIRPE would decrease postoperative opioid use and length of stay (LOS). MATERIALS AND METHODS: A multicenter retrospective cohort study of 20 US children's hospitals was conducted of children (age below 18 years) undergoing MIRPE from January 1, 2014, to August 1, 2019. Differences in total postoperative, inpatient, oral morphine equivalents per kilogram, and 30-day LOS between patients who received cryoanalgesia versus those who did not were assessed using bivariate and multivariable analysis. P value <0.05 is considered significant. RESULTS: Of 898 patients, 136 (15%) received cryoanalgesia. Groups were similar by age, sex, body mass index, comorbidities, and Haller index. Receipt of cryoanalgesia was associated with lower oral morphine equivalents per kilogram (risk ratio=0.43, 95% confidence interval: 0.33-0.57) and a shorter LOS (risk ratio=0.66, 95% confidence interval: 0.50-0.87). Complications were similar between groups (29.8% vs 22.1, P =0.07), including a similar rate of emergency department visit, readmission, and/or reoperation. CONCLUSIONS: Use of cryoanalgesia during MIRPE appears to be effective in lowering postoperative opioid requirements and LOS without increasing complication rates. With the exception of preoperative gabapentin, other adjuncts appear to increase and/or be ineffective at reducing opioid utilization. Cryoanalgesia should be considered for patients undergoing this surgery.

Prospective evaluation of an evidence-based decision tool to assess pediatric blunt abdominal trauma (BAT).

PURPOSE: Computed tomography (CT) is currently the standard for evaluation of intra-abdominal injury (IAI) after BAT. Pediatric patients receiving CT scans based on adult clinical protocols are potentially exposed to unnecessary radiation. The purpose of this study is to determine the rate of CT scans before and after implementation of a pediatric BAT decision tool. METHODS: We adapted and implemented an evidence-based decision tool for pediatric BAT based on five clinical variables. We reviewed patient charts 18 months pre- and post-implementation. Demographics and outcomes were compared using Chi-square and Fisher's exact test, accordingly. RESULTS: The pre and post-implementation groups were uniform when comparing age, sex, mechanism, and Injury Severity Score. The decision tool was utilized in 85% of patients post-implementation. Fewer CT scans were obtained in the post-implementation group (28 vs. 21%, p = 0.215) with no missed injuries or late diagnoses. CONCLUSION: Implementation of a pediatric BAT decision tool decreased CT usage and radiation exposure without an obvious compromise to patient care. This experience supports the utilization of these tools for the assessment of IAI after BAT and have resulted in more selective use of CT during pediatric BAT in our program.

Impact of Clostridium difficile infection on pediatric appendicitis.

INTRODUCTION: Clostridium difficile is an important cause of nosocomial infection in the pediatric population. The purpose of this study is to estimate the impact of Clostridium difficile infection complicating pediatric acute appendicitis. METHODS: This study utilizes the combined 2009 and 2012 Kids' Inpatient Database. Statistical analysis is weighted and was done using Survey Sampling and Analysis procedures in SAS 9.4. RESULTS: We identified 176,934 cases with appendicitis and 0.2% (n = 358) had a concurrent diagnosis of C. difficile. The proportion of cases with C. difficile in perforated appendicitis was greater than in the non-perforated cases (0.39% vs. 0.06%; p < .01). Multivariate analysis showed that perforated appendicitis (OR 5.22), and anemia (OR 4.95) were independent predictors of C. difficile infection (p < .001). Adjusted for perforated appendicitis, cases with C. difficile had 4.78 days longer length of stay (LOS) and higher total charges of $29,887 (all p < 0.0001) compared to non-C. difficile cases. CONCLUSION: C. difficile infection is a rare, but impactful complication of pediatric appendicitis and is associated with greater disease severity. Proper antibiotic stewardship could minimize the risk of C. difficile in pediatric appendicitis.

Short-term surgical trips: local collaboration and its effects on complications and patient satisfaction.

PURPOSE: Short-term surgical missions can provide communities in need with desired expertise; however, it is uncertain who will manage the complications after visiting experts leave. Poor outcomes, decreased patient satisfaction, and tension on the healthcare system develop when local providers, often excluded from the initial patient care, are unable to cope with subsequent morbidity. METHODS: Two-year retrospective review of pediatric general, plastic, and reconstructive surgery, and urology cases performed by a relief organization in the developing world. Case complexity and postoperative complications were analyzed. Phone interviews conducted with patients/families to quantify postoperative outcomes and satisfaction. RESULTS: 474 surgeries were performed on pediatric patients with 60% response rate. Respondents stratified into three levels of complexity: 159 simple, 72 intermediate, and 54 advanced surgeries. Six (2.1%) high-level complications occurred. No association between the complexity of the surgery and the occurrence of a complications. 83.5% were satisfied with outcomes and > 92% were happy with the provided support. CONCLUSION: Facilitating visiting and local surgeons performing cases together increases the expertise of local providers, strengthens infrastructure, and establishes clear follow-up. Despite complications, patients and families continued to recommend care to family and friends by the relief organization and were happy with support from local providers. Engaging local providers is the gold-standard for short-term trips.

Laparoscopic Repair of Pediatric Femoral Hernias.

Background: Current rates of reported pediatric femoral hernias remain exceedingly low, with their incidence reported to be <1%. The mainstay of repair has traditionally been through an open approach, and pediatric surgeons remain reluctant to repair otherwise. Owing to its rarity, consensus regarding management remains absent. Because of this, we present a scoping review on the use of laparoscopy and minimally invasive techniques to repair pediatric femoral hernias. Methods: A scoping literature review was performed using PubMed, Embase, Scopus, and Web of Science for related articles (keywords). Full-text articles and abstracts were then reviewed for relevance using inclusion and exclusion criteria with data extracted from each piece. Results: The search identified 268 articles published from 1992 to 2023. Eleven articles met our inclusion criteria. After reviewing their content, a total of 87 patients were identified. Of these, 42 laparoscopic repairs were reported. Three primary laparoscopic surgical techniques were described, with no recurrence reported. Conclusion: Laparoscopy remains a viable tool in diagnosing and managing femoral hernias. Various technically feasible options for laparoscopy and minimally invasive techniques have been described with excellent results and limited recurrence. However, given the quality of the data, further studies are needed to investigate the long-term durability of such repairs.

Spontaneous Pneumomediastinum is Not Associated With Esophageal Perforation: Results From a Retrospective, Case-Control Study in a Pediatric Population.

What is the optimal management of spontaneous pneumomediastinum (SPM) and is there a risk of esophageal perforation in patients with SPM? We performed a retrospective case-control study of children through age 21, diagnosed with SPM in one hospital system over 10 years with the primary aim of describing the diagnostic workup, treatment patterns, and clinical outcomes. We hypothesized that SPM is a self-limited disease and is not associated with esophageal injury. Cases were identified using International Classification of Disease codes and excluded for trauma or severe infections. Median age was 16 years, 66% were male (n = 179). Chest radiography was performed in 97%, chest computed tomography (CT) in 33%, and esophagrams in 26%. Follow-up imaging showed resolution in 83% (mean = 17.2 days). SPM was not associated with esophageal perforation. We recommend avoiding CT scans and esophagrams unless there is discrete esophageal concern. Management of SPM should be guided by symptomatology.

The Evolving Effectiveness of Biologics in Avoiding Surgery in Children With Ulcerative Colitis: At what Nutritional Cost?

BACKGROUND: Pediatric ulcerative colitis (UC) treatment has changed dramatically with the introduction of multiple biologics. The goal of this study was to determine the effectiveness of these new biologics on achieving remission, nutritional impact, and eventual need for surgery in children. METHODS: We retrospectively analyzed hospital records of UC patients (ages 1-19) seen at a pediatric gastroenterology clinic between January 2012 andAugust 2020. Patients were divided into groups: 1) medically without biologics or surgery; 2) patients treated with one biologic; and 3) patients treated with multiple biologics 4)patients that underwent colectomy. RESULTS: There were 115 UC patients with a mean follow-up of 5.9 ± 3.7 years (1 month-15.3 years). PUCAI score at diagnosis was mild in 52 patients (45%), moderate in 25 (21%), and severe in 5 (4.3%). PUCAI score for 33 patients (29%) could not be calculated. There were 48 (41.3%) in group 1 with 58% remission, 34 (29.6%) in group 2 with 71% remission, 24 (20.8%) in group 3 with 29% remission, and only 9 (7.8%) in group 4 with 100% remission. The majority (55%) of surgical patients had colectomy within the first year of diagnosis. BMI improved after surgery (P = 0.001). The change from one biologic to others did not improve nutrition over time. DISCUSSION: New biologics are changing the landscape in maintaining remission from UC. The current need for surgery is much lower than previously published studies. In medically refractive UC, nutritional status only improved after surgery. Addition of another biologic for medically refractory ulcerative colitis in order to avoid surgery must take into account the positive impact surgery has on nutrition and disease remission.

Management of pediatric appendicitis during the COVID-19 pandemic: A nationwide multicenter cohort study.

BACKGROUND: The COVID-19 pandemic has impacted timely access to care for children, including patients with appendicitis. This study aimed to evaluate the effect of the COVID-19 pandemic on management of appendicitis and patient outcomes. METHODS: A multicenter retrospective study was performed including 19 children's hospitals from April 2019-October 2020 of children (age≤18 years) diagnosed with appendicitis. Groups were defined by each hospital's city/state stay-at-home orders (SAHO), designating patients as Pre-COVID (Pre-SAHO) or COVID (Post-SAHO). Demographic, treatment, and outcome data were obtained, and univariate and multivariable analysis was performed. RESULTS: Of 6,014 patients, 2,413 (40.1%) presented during the COVID-19 pandemic. More patients were managed non-operatively during the COVID-19 pandemic compared to before the pandemic (147 (6.1%) vs 144 (4.0%), p < 0.001). Despite this change, there was no difference in the proportion of complicated appendicitis between groups (1,247 (34.6%) vs 849 (35.2%), p = 0.12). COVID era non-operative patients received fewer additional procedures, including interventional radiology (IR) drain placements, compared to pre-COVID non-operative patients (29 (19.7%) vs 69 (47.9%), p < 0.001). On adjusted analysis, factors associated with increased odds of receiving non-operative management included: increasing duration of symptoms (OR=1.01, 95% CI: 1.01-1.012), African American race (OR=2.4, 95% CI: 1.3-4.6), and testing positive for COVID-19 (OR=10.8, 95% CI: 5.4-21.6). CONCLUSION: Non-operative management of appendicitis increased during the COVID-19 pandemic. Additionally, fewer COVID era cases required IR procedures. These changes in the management of pediatric appendicitis during the COVID pandemic demonstrates the potential for future utilization of non-operative management.

Fetus in fetu: use of intraoperative ultrasound for safe excision of a rare entity.

A prenatally diagnosed abdominal mass at 36 weeks and 0 days was further characterised by postnatal ultrasound and MRI to be likely a rare case of fetus in fetu in an otherwise healthy male. Due to close proximity to both the coeliac axis and superior mesenteric artery (SMA), surgical excision was delayed for several months. Interim CT with intravenous contrast performed at 2 months of age demonstrated the SMA travelling through the posterior aspect of the mass. Surgery proceeded at 2 months of age. Intraoperative ultrasound was used to definitively identify both the coeliac axis and SMA in order to facilitate a safe excision. The patient recovered well with an uneventful discharge to home on postoperative day 8. Pathology confirmed the diagnosis of fetus in fetu.

Clostridioides difficile infection after appendectomy: An analysis of short-term outcomes from the NSQIP database.

BACKGROUND: Clostridioides difficile infection can be a significant complication in surgical patients. The purpose of this study was to describe the incidence and impact on outcomes of Clostridioides difficile infection in adult patients after appendectomy. METHODS: The American College of Surgeons National Surgical Quality Improvement Program data set was used to identify all patients with the primary procedure code of appendectomy between 2016 and 2018. Patient demographics and clinical characteristics were extracted from the database, and descriptive statistics were performed. A multivariate logistic regression was created to identify predictors of Clostridioides difficile infection following appendectomy. RESULTS: A total of 135,272 patients who underwent appendectomy were identified, and of those, 469(0.35%) developed Clostridioides difficile infection. Patients with Clostridioides difficile infection were more likely to be older (51.23 vs 40.47 years; P < .0001), female (P = .004), American Society of Anesthesiology score >2 (P < .0001), present with septic shock (P < .0001), or lack functional independence (P < .0001). Patients with Clostridioides difficile infection were more likely to have increased operative time (62.9 vs 50.4 minutes; P < .0001), have perforated appendicitis (48.9% vs 23.5%; P < .0001), and underwent open surgery (7.0% vs 4.0%; P = .0006). Postoperatively, patients with Clostridioides difficile infection required a longer length of stay (4.8 vs 1.8 days; P < .0001), had increased mortality (2.1% vs 0.1%; P < .0001), higher incidences of postoperative abscess (14.9% vs 2.9%; P < .0001), postoperative sepsis (15.1% vs 4.0%; P < .0001), and readmission (30.7% vs 3.4%; all P < .0001). On multivariate analysis, older age (P < .0001), female sex (P = .0043), septic shock (P = .0002), open surgery (P = .037), and dirty wound class (P = .0147) were all independently predictive factors of Clostridioides difficile infection after appendectomy. CONCLUSION: Clostridioides difficile infection is an uncommon postoperative complication of appendectomy and is associated with worse outcomes and higher mortality. Older patients, female sex, those with sepsis, and those undergoing open surgery are at higher risk for developing Clostridioides difficile infection.

Preoperative Splenic Artery Embolization for Massive Splenomegaly in Children: A Single Center Experience.

Introduction: Massive splenomegaly in children can complicate minimally invasive splenectomy. Splenic artery embolization (SAE) before splenectomy has been shown to decrease splenic volume, reduce intraoperative blood loss, and decrease conversion rates in laparoscopic surgery. Our objective was to review our recent experience with immediate preoperative SAE in massive splenomegaly for pediatric patients using both laparoscopic and robotic techniques. Materials and Methods: We retrospectively reviewed preoperative SAE outcomes in pediatric patients with massive splenomegaly undergoing minimally invasive splenectomy between January 2018 and July 2021. Results: Four patients, 3 female, ages 5-18 years, had SAE immediately before minimally invasive splenectomy. Two cases were completed robotically, one laparoscopically, and one laparoscopic case required conversion to open. SAE time ranged from 69 to 92 minutes. Time between embolization and surgical start ranged from 26 to 56 minutes, with operative times from 153 to 317 minutes. Estimated blood loss ranged from <10 to 150 mL. Mean length of stay was 3.5 days (range 2-6). Postoperative complications included one patient with ileus and another with concurrent gastritis and urinary tract infection. Splenic size comparisons were difficult to perform due to morselization of the spleen; however, excised spleen weights, measurements, and surgeon's impression suggested decreased size of the spleen after SAE. There were no transfusions, postembolization complications, or deaths. Conclusion: SAE subjectively appears to decrease splenic distension, which should allow for easier manipulation and possibly better visualization of splenic hilar vessels during minimally invasive surgery. Immediate preoperative SAE is safe and feasible and should be considered in pediatric patients with massive splenomegaly.

Hand ischemia associated with elbow trauma in children.

OBJECTIVES: Previous observational studies suggest that children with hand ischemia following elbow trauma can be safely observed if Doppler signals are present in the wrist arteries (pink pulseless hand, PPH). Nonoperative management of PPH is predicated on the assumption that PPH results from local arterial spasm, but the mechanism of arterial compromise has not been investigated. We hypothesized that PPH signifies a brachial artery injury that requires surgical repair. METHODS: Retrospective review of operations performed on children with hand ischemia following elbow trauma at a level I trauma center pediatric hospital. RESULTS: Between 2003 and 2010, 12 children (seven males, mean age 7.4 years) underwent brachial artery exploration for hand ischemia following elbow trauma (11 supracondylar fractures, one elbow dislocation) due to falls (n = 10) or motor vehicle crashes (n = 2). At presentation, three subjects had normal radial pulses, eight subjects had Doppler signals but no palpable pulses, and one had weak Doppler flow with advanced hand ischemia. Six of the nine subjects without palpable pulses also had neurosensory changes. All 12 subjects underwent brachial artery exploration either initially (n = 2) or following orthopedic fixation (n = 10) due to persistent pulselessness. At operation, eight of 12 patients (67%) had focal brachial artery thrombosis due to intimal flaps, and four had brachial artery and median nerve entrapment within the pinned fracture site. At discharge, all 12 subjects had palpable radial pulses, but three with entrapment had dense median nerve deficits. One of the three subjects with dense neurologic deficit had complete recovery of neurologic function at ten months. The other two subjects had residual median nerve deficits with partial recovery at 5 and 6 months follow-up, respectively. No patient developed Volkman's contracture. CONCLUSIONS: Brachial artery injuries should be anticipated in children with hand ischemia associated with elbow trauma. Neurovascular entrapment at the fracture site is a possible complication of orthopedic fixation. Absence of palpable wrist pulses after orthopedic fixation should prompt immediate brachial artery exploration. PPH should not be considered a consequence of arterial spasm in these patients.

Analysis of Instrument Motion and the Impact of Residency Level and Concurrent Distraction on Laparoscopic Skills.

OBJECTIVE: Using a laparoscopic box trainer fitted with motion analysis trackers and software, we aim to identify differences between junior and senior residents performing the peg transfer task, and the impact of a distracting secondary task on performance. DESIGN: General surgery residents were asked to perform the laparoscopic peg transfer task on a trainer equipped with a motion tracker. They were also asked to perform the laparoscopic task while completing a secondary task. Extreme velocity and acceleration events of instrument movement in the 3 rotational degrees of freedom were measured during task completion. The number of extreme events, defined as velocity or acceleration exceeding 1 SD above or below their own mean, were tabulated. The performance of junior residents was compared to senior residents. SETTING: Simulation learning institute, Beaumont Hospital, Royal Oak, Michigan. PARTICIPANTS: Thirty-seven general surgery residents from Beaumont Hospital, Royal Oak. RESULTS: When completing the primary task alone, senior residents executed significantly fewer extreme motion events specific to acceleration in pitch (16.63 vs. 20.69, p = 0.04), and executed more extreme motion events specific to velocity in roll (16.14 vs. 15.11, p = 0.038), when compared to junior residents. With addition of a secondary task, senior residents had fewer extreme acceleration events specific to pitch, (14.69 vs. 22.22, p < 0.001). CONCLUSIONS: While junior and senior residents completed the peg transfer task with similar times, motion analysis identified differences in extreme motion events between the groups, even when a secondary task was added. Motion analysis may prove useful for real-time feedback during laparoscopic skill acquisition.

Cost-Effective Approach to the Laparoscopic Appendectomy : Balancing Disposable Instrument Cost With Operative Time.

BACKGROUND: Surgeons can help reduce health care spending by selecting affordable and efficient instruments. The laparoscopic appendectomy (LA) is commonly performed and can serve as a model for improving health care cost. METHODS: We retrospectively reviewed all adult patients who underwent LA for non-perforated appendicitis from March 2015 to November 2017. Our objective was to determine which combination of disposable instruments afforded the lowest total operative cost without compromising postoperative outcomes. RESULTS: In total, 1857 consecutive patients were reviewed from 2 hospitals. After determining the 8 most commonly utilized combinations of disposable instruments, 846 patients were ultimately analyzed. The combination of a LigaSure, Endoloop, and an EndoBag (LEB) had the shortest median operative time (25 minutes, P < .001) and lowest median total operative cost ($1893, P < .001). CONCLUSIONS: The LEB instrument combination rendered the shortest operative time, lowest total operative cost, and can be used to maximize surgical value during LA.

Factors influencing choice of medical vs. surgical treatment of pediatric appendicitis.

PURPOSE: To examine what proportion of caregivers, if given a choice, would choose medical versus surgical treatment of appendicitis and what factors would be important in their decision. METHODS: A survey was devised and given to the caregivers of children presenting to the pediatrician for a routine visit in community and academic pediatric clinics. The survey presented a summary of outcomes after medical (non-operative) and surgical treatment of uncomplicated appendicitis. Participants were then asked to choose medical versus surgical treatment if their child were to develop appendicitis. They were also asked to rate the importance of certain factors in their decision -1 being "not important" and 5 being "very important". RESULTS: Four hundred surveys were distributed with an 86.2% (345/400) response rate. Six percent (21/342) of respondents reported a history of appendicitis and 49.4% (168/340) reported having known someone who had appendicitis. The majority of respondents, 85.3% (284/333), were mothers. A minority of respondents, 41.7% (95% CI: 36.7, 47.0), chose medical treatment over surgery for appendicitis. There was no statistical difference in the proportion of mothers (41.6%) versus fathers who chose medical treatment (41.3%). Caregivers who chose medical treatment were more likely to rate time in hospital (p = .008) and time out of school (p = 05) as important in decision making when compared with those who chose surgery. Those who chose surgical treatment were more likely to rate risk of recurrent appendicitis (p < .001) as important to decision making. In the multivariate analysis, those who rated time in hospital as very important had more than twice the odds of choosing medical therapy (OR 2.20, p = 0.02) when compared with those who rated it as less important. Not knowing someone who has had appendicitis was significantly associated with choosing medical therapy when compared with those who do know someone who has had appendicitis, OR 2.3, p = .002. Rating pain as very important was also significantly associated with choosing medical therapy, when compared to those rating pain 1-3, OR 3.38, p = .03. CONCLUSIONS: In this survey of caregivers of children presenting for routine care, 41.7% would choose medical, or non-operative, therapy for their children with acute appendicitis. The risk of recurrence, time in hospital, and time out of school, pain, and knowing someone who has had appendicitis were all important factors that families may consider when making a decision. These data may be useful for surgeons counseling patients on which treatment to pursue.

Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis.

There is increasing recognition that a major pathophysiologic event in sepsis is the progression to an immunosuppressive state in which the host is unable to eradicate invading pathogens. Although there are likely numerous causes for the immunosuppression, expression of negative costimulatory molecules on immune effector cells is a likely contributing factor. PD-1 is a recently described, negative costimulatory molecule that has potent effects to inhibit T cell activation, cytokine production, and cytotoxic functions. PD-1 plays a critical role in the host response to specific pathogens, but relatively little work has been done on the possible effects of PD-1 in sepsis. We hypothesized that the anti-PD-1 antibody would improve survival in sepsis. Mice underwent CLP, and PD-1 expression was quantitated. Additionally, the effects of anti-PD-1 antibody on lymphocyte apoptosis, cytokine production, host immunity, and survival were determined. PD-1 expression increased beginning 48 h after sepsis, and >20% of CD4 and CD8 T cells were positive by 7 days. Anti-PD-1 antibody administered 24 h after sepsis prevented sepsis-induced depletion of lymphocytes and DCs, increased Bcl-xL, blocked apoptosis, and improved survival. Anti-PD-1 also prevented the loss in DTH, a key indicator of immunocompetence in sepsis. Thus, delayed administration of anti-PD-1 antibody, an important therapeutic advantage, was effective in sepsis. Furthermore, these results add to the growing body of evidence that modulation of the positive and negative costimulatory pathways on immune cells represents a viable therapeutic approach in reversing immunosuppression and improving sepsis survival.

Targeted delivery of siRNA to cell death proteins in sepsis.

Immune suppression is a major cause of morbidity and mortality in the patients with sepsis. Apoptotic loss of immune effector cells such as CD4 T and B cells is a key component in the loss of immune competence in sepsis. Inhibition of lymphocyte apoptosis has led to improved survival in animal models of sepsis. Using quantitative real-time polymerase chain reaction of isolated splenic CD4 T and B cells, we determined that Bim and PUMA, two key cell death proteins, are markedly upregulated during sepsis. Lymphocytes have been notoriously difficult to transfect with small interfering RNA (siRNA). Consequently a novel, cyclodextrin polymer-based, transferrin receptor-targeted, delivery vehicle was used to coadminister siRNA to Bim and PUMA to mice immediately after cecal ligation and puncture. Antiapoptotic siRNA-based therapy markedly decreased lymphocyte apoptosis and prevented the loss of splenic CD4 T and B cells. Flow cytometry confirmed in vivo delivery of siRNA to CD4 T and B cells and also demonstrated decreases in intracellular Bim and PUMA protein. In conclusion, Bim and PUMA are two critical mediators of immune cell death in sepsis. Use of a novel cyclodextrin polymer-based, transferrin receptor-targeted siRNA delivery vehicle enables effective administration of antiapoptotic siRNAs to lymphocytes and reverses the immune cell depletion that is a hallmark of this highly lethal disorder.