Necrotising Myofasciitis of the Lower Limb Secondary to Extra-Peritoneal Rectal Perforation.

Necrotising fasciitis (NF) is a severe and life-threatening soft tissue infection that often requires extensive debridement and reconstruction. Isolated extra-peritoneal rectal perforations due to trauma, cancer, inflammatory bowel pathology or iatrogenically induced can rarely cause necrotising fasciitis beyond the perineum. Given its rarity, there is a high threshold of suspicion which often leads to late recognition and poor outcome. We present a case of necrotising myofasciitis of the right lower limb following occult rectal perforation sustained during elective flexible sigmoidoscopy, and augment this case report with a literature review to guide diagnostics, intervention, and recovery. Therefore, the aim of this work was to review, compile, analyse, and present clinical details to identify masquerading presentations and determine the optimal treatment regimen. A search of PubMed, Scopus, Ovid, MEDLINE, EMBASE, CINAHL Plus, AMED, Web of Science (Science Citation Index), and Google Scholar was supplemented by hand searching. Data extracted included demographics, patient management, and outcome. Of 104 citations identified by a systematic literature search, eight case reports of eight subjects with necrotising fasciitis of the lower limb secondary to rectal perforation met the criteria for analysis. The most common treatment modality was surgical debridement in all cases and bilateral above knee amputation in one case, disarticulation of the lower limb was the treatment in this case we report. Furthermore, faecal diversion by the formation of de-functioning colostomy was performed in the same setting for four (50%) of the patients and appeared to increase survival. Overall 45 days mean (S.E.) disease-specific survival was found to be 32.8 (7.0) days. There is an insufficient number of cases reported to date to confer a significant survival advantage between having a defunctioning colostomy in the same setting as the debridement as opposed to having it at a later setting or not having it at all (Mantel-Cox p=0.1). In summary, a review of all the cases in the literature suggests that NF of lower limbs can be an atypical presentation of rectal cancer, pathology, and/or trauma. We report a case of unilateral lower limb NF secondary to rectal perforation in a non-cancer patient, likely due to flexible sigmoidoscopy. Due to the small number of patients, it is inherently difficult to draw firm conclusions however multi-modality management appears to be more effective, with meticulous debridement, defunctioning of the bowel and downstaging radiotherapy if required. We recommend a UK-wide, national database/registry for NF that will help gather data and formulate more standardised management guidelines.

Outcomes of pediatric patients with therapy-related myeloid neoplasms.

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs.

Thyroid Storm in Head and Neck Emergency Patients.

BACKGROUND: Thyroid storm is a rare but life-threatening emergency that prompts urgent intervention to halt its potentially disastrous outcomes. There is not much literature available on thyroid storm in head neck trauma and non-thyroid/parathyroid head neck surgery. Due to rarity of thyroid storm in head and neck trauma/surgery patients, its diagnosis becomes challenging, is often misdiagnosed and causes delay in the diagnosis and management. Therefore, the aim of this work was to compile, analyze and present details to develop a consensus and augment available literature on thyroid storm in this group of patients. MATERIALS AND METHODS: A comprehensive literature search of the last 30 years was performed on PUBMED/MEDLINE, EMBASE, CINAHL and Science Citation Index for thyroid storm using MeSH words and statistical analyses were performed. RESULTS: Seven articles describing seven cases of thyroid storm were reviewed. All patients required medical management and one patient (14.3%) required adjunctive surgical management. Burch and Wartofsky Diagnostic criteria for thyroid storm were used in diagnosis of 42% patients. Time of diagnosis varied from immediately upon presentation to formulating a retrospective diagnosis of having a full-blown thyroid storm at 4 days post presentation. It was misdiagnosed and unthought of initially in majority of these cases, (71.4%) were not diagnosed in the first day of hospital stay. CONCLUSION: Early recognition of thyroid storm in head and neck patients markedly reduce morbidity/mortality. Albeit unexpected, it should be ruled out in any symptomatic head and neck trauma or post-surgery patient.

Using liver elastography to diagnose sinusoidal obstruction syndrome in pediatric patients undergoing hematopoetic stem cell transplant.

Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Traditional ultrasound (US) has poor sensitivity and specificity. US shear wave elastography (SWE) is a newer technology that measures liver stiffness. This is a single-institution, prospective cohort study evaluating SWE in patients younger than 21 years who received HSCT from December 2015 through June 2017. SOS was defined using the modified Seattle criteria. Subjects had US with SWE at three scheduled time points. t-tests were used to assess for difference between the groups and ROC curves were generated. Twenty-five patients were included. Five subjects developed SOS. At day +5 HSCT, SOS patients had SWE velocities that increased by 0.25 ± 0.21 m/s compared to 0.02 ± 0.18 in patients without SOS (p = 0.020). At day +14, SOS patients had SWE velocities that significantly increased by 0.91 m/s ± 1.14 m/s compared to 0.03 m/s ± 0.23 m/s in patients without SOS (p = 0.010). SWE SOS diagnosis occurred on average 9 and 11 days before clinical and conventional US diagnosis, respectively. Patients who develop SOS have increased liver stiffness compared to patients who do not develop SOS. SWE changes occur before other imaging and clinical findings of SOS.

Effects of Memantine in a Mouse Model of Postoperative Cognitive Dysfunction.

Persistent impairment in cognitive functioning postoperatively is reported by clinical and animal studies, and is labeled as postoperative cognitive dysfunction (POCD). Evidence points to an exaggerated neuroinflammatory response resulting from peripheral systemic inflammation after surgery, with subsequent cytokine-induced glutamatergic excitotoxicity and synaptic impairment. These immunological changes, among many others, are also observed in Alzheimer's disease. Memantine is an N-methyl-D-aspartate receptor (NMDAR) antagonist commonly used to treat Alzheimer's disease. Surprisingly, little research exists on the role of memantine in preventing POCD. The purpose of this study is to investigate the effects of memantine on a spectrum of cognitive functions postoperatively. Mice were divided into 3 groups and each received treatment for 4 weeks. Placebo groups received a placebo then underwent either a sham procedure or a laparotomy procedure. The memantine group received memantine hydrochloride then underwent a laparotomy procedure. Cognitive tests were performed on postoperative days (POD) 1 and 7. Compared to sham-operated mice, placebo groups that underwent a laparotomy procedure showed impaired memory in the Morris water maze test, higher anxiety-like behavior in the open field and the elevated plus maze tests, increased depression-like behavior in the tail suspension test, and lack of preference for social novelty in the three-chamber test. On the other hand, memantine-treated mice that underwent a laparotomy procedure showed enhanced memory on POD7, improved depression-like behavior on POD1 and POD7, enhanced preference for social novelty on POD1, and no improvement in anxiety-like behavior. These findings suggest a potential protective effect of memantine in mice postoperatively on memory, depression-like behavior, and preference for social novelty.

Consensus Report by the Pediatric Acute Lung Injury and Sepsis Investigators and Pediatric Blood and Marrow Transplant Consortium Joint Working Committees on Supportive Care Guidelines for Management of Veno-Occlusive Disease in Children and Adolescents: Part 2-Focus on Ascites, Fluid and Electrolytes, Renal, and Transfusion Issues.

Even though hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic cell transplantation (HCT), there is paucity of research on the management of associated multiorgan dysfunction. To help provide standardized care for the management of these patients, the HCT Subgroup of the Pediatric Acute Lung Injury and Sepsis Investigators and the Supportive Care Committee of the Pediatric Blood and Marrow Transplant Consortium, collaborated to develop evidence-based consensus guidelines. After conducting an extensive literature search, in part 2 of this series we discuss the management of fluids and electrolytes, renal dysfunction; ascites, pleural effusion, and transfusion and coagulopathy issues in patients with VOD. We consider the available evidence using the GRADE criteria.

Pediatric 8p11 eosinophilic myeloproliferative syndrome (EMS): A case report and review of the literature.

The 8p11 eosinophilic myeloproliferative syndrome (EMS) is an aggressive neoplasm driven by translocation of the fibroblast growth factor receptor 1 and often transforms to leukemias and lymphomas that are refractory to treatment. The first case was identified in 1983, and to date over 70 cases have been reported in the literature. Despite those reports, no consensus exists on management of this condition, and inconsistency in treatment regimens is even more pronounced in the pediatric literature. We report a case of a male infant with the 8p11 EMS, review the published pediatric experience with EMS, and discuss treatment strategies for this enigmatic hematological disorder.

Characteristics of Children With Cancer Discharged or Admitted From the Emergency Department.

BACKGROUND: Emergency department (ED) utilization by children with cancer is poorly understood. Among children with cancer, we explored reasons for ED visits and factors associated with admission within U.S. children's hospitals. METHODS: A retrospective study of the 2011-2013 Pediatric Health Information System (PHIS) was conducted. Eligible ED visits included those within 365 days from the first inpatient encounter with an International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) code for cancer. Patient characteristics and reasons for ED visits were assessed. Factors associated with admission from the ED were examined with multivariable regression. RESULTS: There were 26,770 ED visits by 17,943 children with cancer at 39 children's hospitals during the study period. Half of children with cancer visited the ED within 1 year after their first cancer hospitalization in PHIS. Fifty-six percent of ED visits resulted in admission. Fever or neutropenia accounted for the largest proportion of reasons for visits (34.6%). Risk factors for admission were as follows: "Other" race/ethnicity as compared to white, non-Hispanic (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.2-1.6), history of transplant (OR = 1.7, 95% CI 1.4-2.1), and ED visits reasons including neutropenia (OR = 43.4, 95% CI 36.0-52.3), blood stream infection (OR = 3.3, 95% CI 2.8-3.9), pancytopenia (OR = 28.8, 95% CI 18.1-45.9), dehydration (OR = 2.3, 95% CI 1.9-2.9), or pneumonia (OR = 3.8, 95% CI 2.8-5.1). CONCLUSIONS: Children with cancer have high ED usage within 1 year after their first cancer hospitalization. Age, demographic factors, and reasons for ED visits significantly impacted admission from the ED. Further research should focus on ED utilization among children with cancer.

Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure.

A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n = 81). The indication for second HCT was graft failure after the first HCT. Transplantations were performed between 1990 and 2012. The timing of the second HCT predicted subsequent graft failure and survival. Graft failure was high when the second HCT was performed less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between the first HCT and second HCT was less than 3 months, compared with 23% when the interval was longer (P < .001). Consequently, the 1-year survival rate was substantially lower when the interval between the first and second HCTs was less than 3 months compared with longer (23% vs 58%; P = .001). The corresponding 5-year probability of survival was 16% and 45%, respectively (P = .006). Taken together, these data suggest that fewer than one-half of patients with FA undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to reduce the rate of graft failure after first HCT.

Childhood cancer for the primary care physician.

Childhood cancer is rare among childhood diseases and requires a high index of suspicion by the primary care physician to entertain the possibility of cancer when managing common childhood diseases. This article presents an overview of common pediatric cancers, their presentations, and how the primary care physician can work up patients whom they suspect have a malignancy. The goal is to help primary care doctors in early recognition and appropriate referral of patients, in order for patients to receive required specialized care in a timely manner.

Caregiver survey results related to handling of oral chemotherapy for pediatric patients with acute lymphoblastic leukemia.

BACKGROUND: Oral chemotherapy is commonly administered in the home; however, there may be harmful effects on healthy individuals who handle these medications. Caregivers of pediatric patients were surveyed to establish educational needs for safe handling of oral chemotherapy agents. METHODS: An 11-question self-report survey was developed to characterize handling practices for patients in maintenance therapy for acute lymphoblastic leukemia related to caregiver education, use of protective gear, preparation, and disposal of oral chemotherapy agents. RESULTS: Fifty questionnaires were collected. Seventy-two percent of responders reported receiving instruction on safe handling of oral chemotherapy. Ninety percent of responders reported that they did not utilize protective gear during preparation of oral chemotherapy. Although tablet crushers were designated for use with oral chemotherapy by 61% of responders, 22% used the same device to crush other nonchemotherapy medications. The majority of responders disposed of medication waste with regular garbage or poured the remainder down the sink. CONCLUSIONS: Caregiver survey responses demonstrated that personal safeguards were not routinely utilized by pediatric caregivers while handling oral chemotherapy. Future educational efforts should be directed to improve caregiver understanding related to the use of protective equipment, designation of supplies for use with chemotherapy agents, and safe disposal.

Thrombotic microangiopathies.

Thrombotic microangiopathy results from thrombotic occlusion of the microvasculature leading to fragmentation of red blood cells, profound thrombocytopenia, and a microangiopathic hemolytic anemia with elevation of lactate dehydrogenase and negative direct Coomb's test. This constellation of clinical and laboratory findings is not due to one disease entity; rather, it represents a variety of underlying diagnoses. Among the major disease entities are TTP/HUS, which can be congenital or acquired, bacterial infections, medications, vascular or endothelial pathology like Kasabach-Merritt phenomenon, and stem cell transplantation. In this paper, we offer a review of some of the major causes of thrombotic microangiopathy.

Hematopoietic stem cell function in a murine model of sickle cell disease.

Previous studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model. In vitro colony-forming assays showed a significant decrease in progenitor colony formation derived from sickle compared to control bone marrow (BM). Sickle BM possessed a significant decrease in the KSL (c-kit(+), Sca-(1+), Lineage(-)) progenitor population, and cell cycle analysis showed that there were fewer KSL cells in the G(0) phase of the cell cycle compared to controls. We found a significant increase in both lipid peroxidation and ROS in sickle-derived KSL cells. In vivo analysis demonstrated that normal bone marrow cells engraft with increased frequency into sickle mice compared to control mice. Hematopoietic progenitor cells derived from sickle mice, however, demonstrated significant impairment in engraftment potential. We observed partial restoration of engraftment by n-acetyl cysteine (NAC) treatment of KSL cells prior to transplantation. Increased intracellular ROS and lipid peroxidation combined with improvement in engraftment following NAC treatment suggests that an altered redox environment in sickle mice affects hematopoietic progenitor and stem cell function.

Prognostic factors in pediatric acute myeloid leukemia.

Acute myeloid leukemia (AML), a heterogeneous group of diseases with variable responses to the same therapy, comprises nearly a quarter of childhood acute leukemias. Although historically very few prognostic markers have been incorporated into therapeutic decision making in AML, recent advances in technology have enabled identification of numerous factors associated with disease outcome. This review provides a detailed analysis of most clinically relevant factors associated with disease outcome in childhood AML.

Severe autoimmune hemolytic anemia after unrelated umbilical cord blood transplant for familial hemophagocytic lymphohistiocytosis: significant improvement after treatment with rituximab.

A 4-month-old girl diagnosed with familial hemophagocytic lymphohistiocytosis underwent a matched unrelated, umbilical cord blood transplant. Six weeks later she developed severe acute autoimmune hemolytic anemia and thrombocytopenia requiring multiple transfusions. This was refractory to high-dose steroid and intravenous immunoglobulin, but did respond to Rituximab (anti-CD20 monoclonal antibody) 375 mg/m2. Hemolysis recurred after steroid tapering but responded to a second course of Rituximab. This case report highlights the difficulty in managing posttransplant autoimmune hemolytic anemia.