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Introduction: Carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) are a widely used high-dose chemotherapy regimen for autologous stem cell transplantation transplant (ASCT) in lymphoid malignancies. During BCNU shortages, some centers switched to fotemustine-substituted BEAM (FEAM). Neutropenic enterocolitis (NEC) is a life-threatening complication occurring after intestinal mucosa damage related to intensive chemotherapy. NEC mortality may be up to 30%-50%. In our study, we compared NEC incidence, symptoms, mortality, and transplant outcome in terms of overall survival (OS) and progression-free survival (PFS) in the BEAM vs. FEAM groups. Furthermore, we compared the cost of hospitalization of patients who did vs. patients who did not experience a NEC episode (NECe). Methods: A total of 191 patients were enrolled in this study (N = 129 and N = 62 were conditioned with BEAM and FEAM, respectively). All patients received bed-side high-resolution ultrasound (US) for NEC diagnosis. Results and discussion: NEC incidence and NEC-related mortality were similar in the BEAM and FEAM groups (31% and 40.3%, p = 0.653, and 5% and 8%, p = 0.627, respectively). At a median follow-up of 116 months, no difference was noted between BEAM vs. FEAM groups in terms of OS and PFS (p = 0.181 and p = 0.978, respectively). BEAM appeared equivalent to FEAM in terms of NEC incidence and efficacy. The high incidence of NEC and the low mortality is related to a timely US diagnosis and prompt treatment. US knowledge in NEC diagnosis allows to have comparable days of hospitalization of patients NECpos vs. patients NECneg. The cost analysis of NECpos vs. NECneg has been also performed.

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Cancer is the second most common cause of death worldwide. Bowel emergencies in patients with cancer are becoming increasingly more prevalent due to advances in cancer therapy and longer overall patient survival. When these patients present acutely, they are often frail and may have pre-existing co-morbidities. This article discusses the imaging features of bowel emergencies commonly encountered in oncological patients in clinical practice. These include chemotherapy related colitis, neutropenia enterocolitis and typhlitis, toxic megacolon, bowel perforation, malignant bowel obstruction and gastrointestinal haemorrhage. The radiologist plays a key role in identifying these oncological emergencies and guiding further management.

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BACKGROUND: The use of certain chemotherapy agents is associated with the development of a condition called "chemotherapy-associated neutropenic enterocolitis" (CANE). OBJECTIVE: To determine the risk of CANE associated with the use of each antineoplastic agent. METHODS: The FDA FAERS database of spontaneous adverse reactions was searched for the occurrence of the MedDRA preferred term "neutropenic colitis." RESULTS: The search resulted in 1134 records of patients (535 [47.3%] females, 479 [42.2%] males, sex not specified in 120 [10.6%]) with neutropenic colitis receiving immunosuppressive chemotherapy. The mean age of patients was 47 (SD 22). 22 antineoplastic agents were found to have a strong association (reported odds ratio [ROR] > 100) with the occurrence of CANE; 9 had ROR < 2. CONCLUSION: Drug databases have several limitations in providing updated information about newly approved pharmaceutical adverse events. Signal detection is a diagnostic method recognized as practical in pharmacovigilance. It may be utilized in the FDA's adverse event reporting database and has demonstrated a reasonable predictive performance in signaling adverse events. Our study emphasized the substantial knowledge gap between what we know about the potential risk of CANE caused by antineoplastic agents and the reports of the FDA on their new approved products.

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BACKGROUND/AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with the functional impairment of multiple joints and the destruction of bone and cartilage. Methotrexate (MTX) is a first-line drug commonly used to treat RA; however, even low doses of MTX can potentially cause rare but severe adverse reactions, such as neutropenic enterocolitis (NE), a life-threatening disease characterized by intestinal mucosal damage and immunodeficiency. CASE REPORT: Here, we report on an 82-year-old RA patient who developed life-threatening NE after ten years of low-dose MTX treatment. The condition of the patient rapidly worsened, requiring emergency electrical cardioversion and intravenous treatment with immunoglobulin (IVIG). Immunophenotypic responses were analyzed before and after treatment to evaluate therapeutic efficacy. CONCLUSION: This case highlights the importance of monitoring elderly patients with RA receiving low-dose MTX treatment for the potential accumulation of MTX toxicity. Our findings also illustrate the importance of providing timely IVIG therapy for MTX-induced NE.

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In this case report, a 53-year-old woman was diagnosed with severe NE after receiving chemotherapy for breast cancer. The patient with breast cancer was treated with a single cycle of docetaxel (140 mg) + epirubicin (130 mg) + cyclophosphamide (0.9 g) chemotherapy. However, the woman presented with symptoms of fatigue and diarrhea 5 days later accompanied with severe neutropenia according to the routine blood test. The computed tomography examination displayed the thickening and swelling of the colorectal wall. After the diagnosis of NE, the woman received antibiotics and supportive treatment, but her symptoms were not improved. The Chinese herbal medicine (CHM) diagnostic pattern was then designed for the patient. The patient was administered with two CHM decoctions. One decoction contained 24 kinds of herbal materials, and the other one was called pure ginseng decoction. These two decoctions were administered to the patient 2 or 3 times per day to tonify the spleen, nourish Qi and blood, and remove phlegm and damp heat symptoms. After the CHM treatment lasting for 10 days, the symptoms of the patient were improved, and she was discharged. In conclusion, CHM treatment played an indispensable role in curing the woman with chemotherapy-induced NE.

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Introduction: Neutropenic enterocolitis (NEC) is a life-threatening complication reported in patients with acute myeloid leukemia (AML) following chemotherapy (CHT). Intensive induction and consolidation CHT may damage intestinal mucosa leading to a NEC episode (NECe). NEC reported mortality may be up to 30-60%. Early US-guided bed-side diagnosis and prompt treatment may substantially improve the survival. An emerging worldwide concern is the intestinal colonization by multi-drug-resistant bacteria especially when patients are exposed to chemotherapy regimens potentially correlated to mucosal damage. Methods: In our study we prospectively enrolled all AML patients admitted in our leukemia unit to receive intensive induction and consolidation chemotherapy and experiencing chemotherapy-induced-neutropenia (CHTN). Results and discussion: Overall, we enrolled N=213 patients from 2007 to March 2023. We recorded N=465 CHTN, and N=42 NECe (9.0% incidence). The aim of our study was to assess which chemotherapy regimens are more associated with NEC. We found that ALM1310, followed by 7 + 3 (daunorubicin), 7 + 3 (idarubicin), 5 + 3 + 3 (cytarabine, etoposide, idarubicin), and AML1310 (consolidation) were associated with a statistically higher incidence of NEC. We did not detect NEC episodes in patients treated with CPX-351, 5 + 2 (cytarabine, idarubicine), and high-dose cytarabine. Thus, we found that cytarabine could determine mucosal damage when associated with an anthracycline but not if delivered either alone or as dual-drug liposomal encapsulation of daunorubicin/cytarabine. We also describe NEC mortality, symptoms at diagnosis, intestinal sites involvement, and prognostic significance of bowel wall thickening.

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Ischemic colitis is thought to be an injury to the colon as a result of reduced blood flow. Certain infectious diseases such as the Epstein-Barr virus can aid in the reduction of blood flow. The insult can range from inflammation and superficial injury to full-thickness necrosis. The typical regions affected are the "watershed" areas of the colon: the splenic flexure, the rectosigmoid junction, and the right colon. Because patients can present with a wide spectrum of symptoms from vague abdominal discomfort to complete abdominal catastrophe, the diagnosis of ischemic colitis is sometimes challenging to make. Patients typically present with the acute onset of crampy abdominal pain and usually pass blood mixed with stool within 24 hours. Endoscopically, ischemia is suspected in the presence of bluish hemorrhagic nodules from submucosal bleeding, cyanotic or necrotic mucosa with bleeding ulcerations, or a segmental distribution with an abrupt transition point between injured and normal mucosa. We present a case of an 80-year-old male with a history of hypertension, hyperlipidemia, and basal cell carcinoma of the scalp diagnosed with ischemic colitis associated with positive Epstein-Barr virus B cell lymphoma.

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Neutropenic enterocolitis (NEC) is a life-threatening condition occurring in severely neutropenic patients, following intensive chemotherapy for leukemia. Its pathogenesis is not entirely understood and believed to be multifactorial, including mucosal injury as a result of cytotoxic drugs, profound neutropenia, impaired host defense and possibly microbiota changes. Establishing an early diagnosis is key. The management of NEC remains undefined due to lack of high-quality clinical data. With a better understanding of the disease, a more conservative approach is preferred over surgical intervention. The involvement of a multi-disciplinary team, consisting of the oncologist, infectious diseases specialists and surgeons is highly recommended. This review aims to delineate insights into the pathophysiology and clinical presentation of NEC and to emphasize the diagnostic and therapeutic approach to this condition.

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BACKGROUND: We aimed to identify prognostic indicators in pneumatosis intestinalis (PI) in a pediatric oncology population. We hypothesized that neutropenia would be an independent risk factor for adverse outcomes, including the need for abdominal operation to treat PI and for the development of recurrent PI. METHODS: We performed a retrospective review of all patients treated for PI between 2009 and 2019 with a diagnosis of cancer or history of bone marrow transplant (BMT). RESULTS: Sixty-eight children were treated for their first episode of PI; 15 (22%) were not neutropenic at presentation; eight underwent urgent abdominal operation (12%). Patients with neutropenia were more likely to receive TPN, had a longer course of NPO, and received a longer course of antibiotics. Neutropenia at presentation was associated with a decreased risk of PI recurrence (40% vs 13%, p = 0.03). Children who required an abdominal operation were more likely to require vasopressors at diagnosis (50% vs 10%, p = 0.013). CONCLUSIONS: Among pediatric cancer patients, need for vasopressors at the time of PI is a marker of severe PI, with increased likelihood of requiring operative intervention. The presence of neutropenia is associated with lower rates of PI recurrence. LEVEL OF EVIDENCE: Level III.

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Neutropenic enterocolitis (NE) is a rare and life-threatening condition that typically occurs in patients with hematologic malignancies undergoing intensive chemotherapy, radiation therapy, or bone marrow transplant regimens, predisposing them to profound neutropenia. NE can have a nonspecific clinical presentation and mimic other gastrointestinal disorders such as appendicitis, diverticulitis, or inflammatory bowel disease but is associated with very high morbidity and mortality if not diagnosed and treated promptly. We present the case of a middle-aged female with a recent diagnosis of follicular lymphoma who developed neutropenic enterocolitis after undergoing induction chemotherapy for an autologous stem cell transplant (ASCT). In this article, we provide a literature review of neutropenic enterocolitis and highlight the importance of a prompt diagnosis and management, given its high mortality rate.

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PURPOSE: Pneumatosis intestinalis (PI) remains difficult to treat as it can lead to a broad range of clinical sequalae and there are little published data available to guide management. Our aim was to evaluate how pediatric surgeons currently manage children with PI, how treatment varies based on etiology, and to identify opportunities to optimize current PI management strategies. METHODS: We administered a web-based survey of practicing pediatric surgeons in the United States and Canada. The survey was distributed to all members of the American Pediatric Surgical Association. RESULTS: Of 1508 distributed surveys, 333 responses were received (22% response rate); 174 were complete and included in analysis (12% analyzed). For all scenarios, respondents recommended treatment for PI include a median 7 days of bowel rest and 7 days antibiotics. Only 41% reported their approach to PI management was optimal. Ways to optimize care include treatment based on etiology (83%), decreased number of repeat images (64%), shorter NPO course (49%), and shorter antibiotic course (47%). CONCLUSION: Pediatric surgeons manage PI similarly regardless of etiology but most report this is suboptimal. Future work is needed to prospectively evaluate management protocols that consider etiology.

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BACKGROUND: Neutropenic enterocolitis (NE), or typhlitis, a condition typically associated with severe neutropenia in the setting of chemotherapy, is highly morbid (50-100%) and benefits from early diagnosis. It has been associated with neutropenia in the setting of human immunodeficiency virus (HIV) but has not been described in a patient with HIV who was not neutropenic on presentation. We present the case of a patient with HIV who was not neutropenic on presentation but found to have NE. CASE PRESENTATION: A 27-year-old male with a history of HIV on antiretroviral therapy and epilepsy presented with concern for breakthrough seizure. The patient revealed he was having non-bloody, non-bilious emesis and diarrhea for 3 days. Initial labs were white blood cell count 3.9 × 109/L, absolute neutrophil count (ANC) 3.14 × 109/L, CD4 count 290 cells/mm3, and undetectable viral load. A computed tomography (CT) scan of the abdomen/pelvis with contrast revealed wall thickening of the cecum and proximal ascending colon (Fig. 1), suggestive of NE. The patient was started on cefepime and metronidazole but switched to piperacillin/tazobactam after he became leukopenic/neutropenic. CONCLUSIONS: Neutropenic enterocolitis, typically presenting with fever, abdominal pain, and hematochezia, can be difficult to identify, particularly in patients without a history of malignancy. However, it should be considered in patients with HIV presenting with these symptoms, even with a normal ANC and CD4 count above 200 cells/mm3. Prompt diagnosis can be made with CT, and early initiation of broad-spectrum antibiotics greatly reduces the risk of morbidity/mortality.

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Neutropenic enterocolitis (NE) is a medical emergency that occurs in neutropenic patients characterized by diffuse circumferential mural thickening predominantly involving the cecum. It is not easily differentiated from various other abdominal conditions (i.e., appendicitis, intussusception, ischemic colitis, small bowel obstruction, pseudomembranous colitis, and viral gastroenteritis), but clinicians should be aware of the diagnostic criteria in order to assist with prompt diagnosis. Although standard treatment has yet to be established, it is necessary to initiate early supportive care to reduce mortality risk. Here we present a case of NE with small bowel obstruction in a patient with acute myeloid leukemia (AML). Clinical findings and CT abdomen/pelvis were consistent with NE. Unfortunately, the patient succumbed to the illness.

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Typhlitis, is also known as neutropenic enterocolitis, affects the cecum and distal ileum. It was frequently encountered in pediatric patients who were undergoing treatment for leukemia. Nonetheless, it can affect adult patients, regardless of the cause of the immunosuppression. We report the case of a 20-year-old patient who was receiving chemotherapy for Osteosarcoma, who had a 6-day history of nausea and vomiting, fever sensation, diarrhea, and diffuse abdominal pain. Physical examination was relevant for hemodynamic instability, a distended and tender abdomen predominantly in the right iliac fossa. The laboratory workup showed severe neutropenia, thrombocytopenia, and electrolyte disturbances. The image studies evidenced edema of the ascending colon and cecum. Treatment was started with vasopressor support, correction of electrolyte alterations, blood cell and platelet transfusion, G-CSF, hydration, broad spectrum antibiotic therapy, initially with adequate clinical and laboratory response. After a few days, he presented lower gastrointestinal bleeding which was treated by conservative management. In conclusion, typhlitis must be suspected in every patient developing neutropenia as a reaction to chemotherapy and who also presents gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and intense abdominal pain.

La tiflitis o también denominada enterocolitis neutropénica afecta el ciego e íleon distal. Fue descrita comúnmente en pacientes pediátricos sometidos a tratamiento para leucemia; sin embargo, puede afectar al paciente adulto independiente de la causa que origine la inmunosupresión. Presentamos el caso de un paciente de 20 años con antecedente de osteosarcoma, quien acude con tiempo de enfermedad de 6 días caracterizado por náuseas y vómitos, sensación de alza térmica, diarrea y dolor abdominal difuso. Al examen físico se encuentra hemodinámicamente inestable, abdomen distendido y se corrobora el dolor abdominal a predominio en fosa iliaca derecha. Los exámenes de laboratorio mostraron neutropenia severa, trombocitopenia y alteraciones hidroelectrolíticas. En los estudios de imágenes la TC evidenció edema de asas delgadas, así como edema de pared del colon ascendente y ciego. Se inició tratamiento con soporte vasopresor, corrección de alteraciones hidroelectrolíticas, transfusión de paquetes globulares y plaquetas, G-CSF, hidratación, terapia antibiótica de amplio espectro, inicialmente con adecuada respuesta clínica y laboratorial. Al cabo de unos días presentó hemorragia digestiva baja como complicación que fue tratada mediante manejo conservador. En conclusión, la tiflitis debe sospecharse en todo paciente que desarrolla neutropenia luego de quimioterapia y que presenta síntomas gastrointestinales como náuseas, vómitos, diarrea y dolor abdominal intenso. El manejo conservador, en pacientes con hemorragia digestiva y tiflitis, que involucra corrección de coagulopatía, transfusión de paquetes globulares e hidratación, puede ser el adecuado en pacientes que no cursan con inestabilidad hemodinámica y logran controlar el sangrado.

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Neutropenic enterocolitis (NE) is a life-threatening complication associated with neutropenia and the main cause of acute abdominal syndrome in neutropenic patients, especially those receiving intensive chemotherapy. This review aims to delineate actual insights into this clinical entity, to emphasize diagnostic and therapeutic management, and to generate hypotheses on pathophysiology to identify avenues for research. Diagnosis is based on the association of neutropenia, fever, abdominal symptoms, and radiologic bowel wall thickening. Main complications are sepsis, perforations, and gastrointestinal bleeding. Several mechanisms may be responsible for mucosal injury: treatment-induced necrosis of the intestinal specific infiltrates, spontaneous intramural hemorrhage, or microvascular thrombosis. The prevailing cause is the direct cytotoxicity of chemotherapy. However, the role of gut dysbiosis in NE remains to be fully elucidated. Therapeutic management includes early multidrug antibiotherapy, transfusion support, hematopoietic growth factor treatment, fluid resuscitation, correction of electrolytes imbalance, and bowel rest. Indication and timing for surgical management are still debated.

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BACKGROUND: Neutropenic enterocolitis is uncommon but potentially life-threatening, with the cornerstone of treatment being medical management (MM), and surgical intervention reserved for clinical deterioration or bowel perforation. We hypothesized that the Shock Index Pediatric Age-Adjusted (SIPA) is elevated in patients who are at greatest risk for surgical intervention and mortality. We also sought to identify computed tomography (CT) findings associated with surgical intervention and mortality. METHODS: A single-center cancer registry was reviewed for neutropenic enterocolitis patients from 2006 -2018. Survival models compared patients with normal versus elevated SIPA throughout their hospitalizations for the time to surgical management (SM), as well as in-hospital mortality. RESULTS: Seventy-four patients with neutropenic enterocolitis were identified; 7 underwent surgery. In-hospital mortality was 12% in MM and 29% in SM; mortality among patients with elevated SIPA was 4.7 times higher compared to those with normal SIPA (95% CI: 1.1, 19.83, p = 0.04). CT findings of bowel obstruction, pneumatosis, and a greater percentage of large bowel involvement were associated with surgical intervention (all ps < 0.05). CONCLUSION: Select pre-operative CT findings were associated with need for operative management. Elevated SIPA was associated with increased mortality. Elevated SIPA in pediatric cancer patients with neutropenic enterocolitis may help to identify those with more severe disease and expedite beneficial interventions.

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BACKGROUND: Bacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis. CASE PRESENTATION: We report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention. CONCLUSION: Mucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.

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(1) Background: Neutropenic enterocolitis (NEC) is a life-threatening complication following chemotherapy with high mortality rates. Early diagnosis is crucial to improve outcomes. We designed a large prospective study employing bedside ultrasonography (US) as a novel approach to allow early diagnosis and prompt treatment to reduce mortality. (2) Methods: NEC was defined as US or computed tomography (CT)-proven bowel wall thickness ≥ 4 mm at the onset of at least one of the following symptoms: fever and/or abdominal pain and/or diarrhea during neutropenia. From 2007 to 2018, 1754 consecutive patients underwent baseline bedside US that was invariably repeated within 12 h from the onset of symptom(s) suggestive of NEC. (3) Results: Overall, 117 episodes of NEC were observed, and overall mortality was 9.4%. Bowel wall thickening was invariably absent in the negative control group. Abdominal pain associated with one or more symptoms correlated with the highest relative risk (17.33), sensitivity (89.7%), specificity (100%), and accuracy (96.2%) for diagnosis. The combination of abdominal pain and fever at onset significantly correlated with worse survival (p < 0.0001, OR 13.85). BWT (p = 0.046), type of therapy (p = 0.049) and blood culture positivity (p = 0.003) correlated with worse survival. (4) Conclusions: Bedside ultrasound is a non-invasive and radiation free imaging technique for early diagnosis of NEC and its prompt treatment significantly reduced mortality.

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Background: Neutropenic enterocolitis (NE), which in the past was also known as typhlitis or ileocecal syndrome for the segment of the gastrointestinal tract most affected, is a nosological entity that is difficult to diagnose and whose pathogenesis is not fully known to date. Initially described in pediatric patients with leukemic diseases, it has been gradually reported in adults with hematological malignancies and non-hematological conditions, such as leukemia, lymphoma, multiple myeloma, aplastic anemia, and also myelodysplastic syndromes, as well as being associated with other immunosuppressive causes such as AIDS treatment, therapy for solid tumors, and organ transplantation. Therefore, it is associated with high mortality due to the rapid evolution in worse clinical pictures: rapid progression to ischemia, necrosis, hemorrhage, perforation, multisystem organ failure, and sepsis. Case report: A case report is included to exemplify the clinical profile of patients with NE who develop sepsis. Literature Review: To identify a specific profile of subjects affected by neutropenic enterocolitis and the entity of the clinical condition most frequently associated with septic evolution, a systematic review of the literature was conducted. The inclusion criteria were as follows: English language, full-text availability, human subjects, and adult subjects. Finally, the papers were selected after the evaluation of the title and abstract to evaluate their congruity with the subject of this manuscript. Following these procedures, 19 eligible empirical studies were included in the present review. Conclusions: Despite the recent interest and the growing number of publications targeting sepsis and intending to identify biomarkers useful for its diagnosis, prognosis, and for the understanding of its pathogenesis, and especially for multi-organ dysfunction, and despite the extensive research period of the literature review, the number of publications on the topic "neutropenic enterocolitis and sepsis" appears to be very small. In any case, the extrapolated data allowed us to conclude that the integration of medical history, clinical and laboratory data, radiological imaging, and macroscopic and histological investigations can allow us to identify a specific pathological profile.

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Achromobacter xylosoxidans,subspecies denitrificans is a rare Gram-negative bacillus that causes health care associated infections in immunocompromised hosts. Carbapenems and anti-pseudomonal penicillins are listed as suitable empiric therapy in the literature. Herein, we report a case of a 77-year-old male with stage IV adenocarcinoma of the lung who presented with and was improving from Salmonella javiana enterocolitis, only to subsequently develop A. xylosoxidans,subspecies denitrificans bacteremia that was resistant to both meropenem and piperacillin-tazobactam. With empiric antibiotic coverage falling short of microbial clearance, timelyin vitrosusceptibility testing and prompt infectious disease consultation are of the utmost importance for treatment.