Neutropenic Enterocolitis in Adults: Case Series and Review of the Literature

Necrotizing enterocolitis in adults is a rare disease and, in the past, has been associated with nearly uniform mortality. In recent years, necrotizing enterocolitis, now termed neutropenic enterocolitis, in adults has become more prevalent as a complication of aggressive systemic chemotherapy. In this report, we discuss two cases of neutropenic enterocolitis secondary to the administration of systemic chemotherapy in adult cancer patients: one with lung carcinoma, the other with leukemia. Both patients were successfully treated with early surgical intervention for resection of all necrotizing enteric lesions, and subsequent aggressive critical care support. Our experience suggests that early surgical intervention in adult patients with intestinal necrosis due to chemotherapy is essential to avoid mortality from this condition. Given the widespread, aggressive use of systemic chemotherapy in the neoadjuvant setting, patients at risk for this potentially lethal complication of neutropenic enterocolitis are increasingly common.     

Diagnosis and Antimicrobial Therapy of Lung Infiltrates in Febrile Neutropenic Cancer Patients

Pulmonary infiltrates develop in up to 25% of febrile neutropenic patients and are frequently refractory to broad-spectrum antibacterial therapy. Etiologically, Aspergillus spp., Pneumocystis jiroveci, multi-resistant Gram-negative rods as well as mycobacteria and respiratory viruses may be involved. Taking into account the predominant role of fungal pathogens, typically without microbiological proof, prompt addition of mold-active systemic antifungal therapy improves clinical outcome, while other microorganisms should typically be targeted based upon microbiological test results only. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their etiological relevance for pulmonary infiltrates. Non-culture based diagnostic procedures to detect circulating antigens such as galactomannan or 1,3-beta-D-glucan, or PCR techniques to amplify DNA from blood, bronchoalveolar lavage or tissue specimens, may facilitate the diagnosis. For pre-emptive antifungal treatment, voriconazole or liposomal amphotericin B are preferred. Antifungal treatment should be continued for at least 14 days before non-response and treatment modification are considered. Primary choice for treatment of Pneumocystis pneumonia remains high-dose trimethoprim-sulfamethoxazole, while cytomegalovirus pneumonia is treated with ganciclovir in the majority of patients affected.     

Combination of Amikacin and either Ampicillin or Cephalotin as Initial Treatment of Febrile Neutropenic Patients

ABSTRACT. A prospective, randomized trial of two antibiotic combinations (amikacin plus either ampicillin or cephalotin) was performed on 39 consecutive episodes of fever in 30 patients with neutropenia and hematological malignancy. Infections were documented as the cause of fever in 37 episodes (95%): in 21 episodes (54%) bacteria or a virus (n=1) were isolated, and in 16 (41% of all episodes) the infection was documented clinically but no pathogen was isolated. The most frequently isolated bacteria were Staph, aureus (38% of all strains), E. coli (13%), and Pseudomonas aeruginosa (13%). Bacteremia occurred in 18% of the febrile episodes. Improvement followed treatment with the combination amikacin plus ampicllin in 73% of 19 cases, and with amikacin plus cephalotin in 55% of 20 cases (p>0.05), giving a total Improvement rate of 64%. Failure of therapy was seen in episodes caused by multiple bacteria or Pseudomonas infections. Mild signs of nephrotoxicity were noted in 13% during both regimens. Audiograms were normal in all but two patients who showed slight high-frequency hearing loss. A second infection occurred in 7 episodes (18%). Thus, the combination of amikacin plus ampidllin was as efficient (but less expensive) as amikacin plus cephalotin in the initial treatment of febrile episodes in neutropenic patients with hematological malignancies.     

Cardiac Rehabilitation: Current Review of the Literature and Its Role in Patients with Heart Failure

Purpose of review

Cardiovascular (CV) disease remains the leading cause of death in the USA despite major advances in its treatment. With time, cardiac rehabilitation (CR) programs have gathered interest to help increase CV health and improve functional status after a CV event. Patients with heart failure have also been shown to benefit. In this review, we will evaluate the current literature showcasing the benefits of CR, particularly in patients with heart failure, discuss current limitations, and avenues for future investigation.

Recent findings

Studies have shown that CR is beneficial in reducing morbidity, mortality, hospitalizations, activity-related symptoms, and increasing quality of life. Similar findings have also been observed in patients with heart failure who underwent CR in addition to optimal medical management.

Summary

The positive effects of CR are well established in patients with coronary disease. Recent literature is also showing a trend to benefit in patients with heart failure, though much of the evidence is limited to patients with systolic dysfunction. Despite recommendations by professional societies, the use of CR remains underutilized. Further investigation is needed to better understand the impact of CR in heart failure. Moreover, strategies to increase CR utilization must be explored.

     

Efficacy and Safety of Caspofungin Treatment in Febrile Neutropenic Patients with Hematological Disorders: A Multicenter Consecutive Case Series

Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient. Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met. Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen. Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.     

The Role of Procalcitonin in Respiratory Infections

Accurate diagnosis, risk stratification, and decisions about the need for and optimal duration of antibiotic therapy are cornerstones of the management of patients with respiratory infections. A growing body of evidence supports the use of procalcitonin, a marker of bacterial infection, in addition to conventional clinical parameters to improve diagnostic and prognostic assessment in patients with suspicion of respiratory infections. In addition, several randomized controlled trials indicate that procalcitonin may be used for clinical decision making about initiation and optimal duration of antibiotic therapy. For patients with respiratory infections, procalcitonin-guided antibiotic therapy resulted in less antibiotic use without any apparent adverse patient outcome. For other infections outcome studies are currently lacking. This review summarizes the results of recent investigations of procalcitonin in respiratory infections to provide physicians an overview of the utility and limitations of procalcitonin when used for bedside decision making.     

The Role of Social Support in Collegiate Recovery Communities: A Review of the Literature

In the past decades one response to the increase of college drinking is the growing prevalence of Collegiate Recovery Communities (CRC). Numerous publications on these programs exist, yet a review does not. With a growing need for evidence-based model programs to address the concerns of alcohol abuse and dependence on college campuses, the importance of a collection on the effectiveness of CRCs exists. The goal of this article is to compile a thorough overview of data on CRCs in the United States, focusing specifically on the role of social support in recovery maintenance. Recommendations for future directions are discussed.     

Short Courses of Intravenous Empirical Antibiotic Treatment in Selected Febrile Neutropenic Children with Cancer

Background: Since the optimal duration of antibiotic therapy in febrile neutropenic patients is not clear, we evaluated the safety and efficacy of short courses of intravenous antibiotic treatment in selected pediatric cancer patients admitted for fever and neutropenia. Patients and Methods: We retrospectively analyzed the clinical course of children with chemotherapy-induced neutropenia and fever. All patients were treated with empirical intravenous antibiotics. In episodes of fever of unknown origin (FUO), treatment regimen allowed discontinuation of antibiotics and early hospital discharge regardless of absolute neutrophil count (ANC) or evidence of bone marrow recovery as long as patients were afebrile for at least 24 h and had been treated for a minimum of 72 h. Results: 106 episodes of febrile neutropenia occurred in 56 patients. 84 episodes were classified as FUO and intravenous antibiotic therapy was discontinued regardless of ANC when patients met the criteria described above. No death or major complication occurred. None of the patients had to be rehospitalized for recurrent fever or infection. Conclusion: Discontinuation of intravenous antibiotics regardless of ANC or evidence of bone marrow recovery seems safe and effective in pediatric cancer patients with FUO when children are afebrile for at least 24 h and are treated for a minimum of 72 h. Received: June 28, 2001 · Revision accepted: October 29, 2001     

Neutrophil Apoptosis in Neutropenic Patients With Hepatitis C Infection: Role of Caspases 3, 10, and GM-CSF

Patients with chronic HCV infection are prone to increased susceptibility bacterial infection due to neutropenia complicating the course of this disease. Neutropenia in those patients may stem from enhanced neutrophil apoptosis. However, the molecular mechanism of neutrophil apoptosis has not been clearly defined. Neutrophils harvested from 26 neutropenic patients with hepatitis C infection and nine age and sex-matched healthy control subjects were examined for the degree of apoptosis. Neutrophil apoptosis was quantified by flow cytometry through determination of annexin-V expression at 0 time (fresh neutrophil), and 24 h culture. Neutrophils from healthy subjects were also incubated with either 10% heterologous normal or neutropenic sera, with and without 10 μg GM-CSF. Caspases 3, 10 were assessed colormetrically in neutrophils at 0 times and after 24 h culture. At 0 time culture the neutrophil apoptosis of the HCV patients was in significantly higher as compared to that of normal control (P = 0.059). At 24 h culture patients neutrophils cultured with neutropenic patients own sera showed neutrophil apoptosis significantly increased as compared to that at 0 time culture and this effect was significantly attenuated in similar culture with addition of GM-CSF (P < 0.001). On the other hand patient’s neutrophil cultured with normal sera showed insignificantly increased neutrophil apoptosis at 24 h culture as compared to that at 0 time culture. Caspases 3 and 10 activities were significantly higher in patients neutrophil after 24 h cultured with patients own sera as compared to 0 time culture (P < 0.001 for both). Addition of GM-CSF to the neutrophil culture down regulates the caspases 3 and 10 activities. The correlation study between annexin-V expression and caspases activities revealed a borderline positive correlation between annexin-V and caspase 3 (r = 0.376, P = 0.058), and significant positive correlation with caspase 10 activity (r = 0.494, P = 0.01). In conclusion, these findings suggest that enhanced neutrophil apoptosis demonstrated in neutropenic patients with HCV infection might be induced through activation of caspase 10 and is attenuated by GM-CSF.     

An Exploration of the Role of MicroRNAs in Psoriasis: A Systematic Review of the Literature

Psoriasis is recently characterized by a specific microRNAs (miRNAs) expression profile, which guides the researchers’ efforts to explore the therapeutic targets and objective biomarkers that reflect the diagnosis and disease activity in clinical use for psoriasis.The paper presents a state-of-the-art review of expression and function of miRNAs in psoriasis along with its clinical implications.We analyzed all literature searched by keywords “microRNA” and “psoriasis” in PubMed (Medline) from inception up to July 2015, and the references in the literature searched were also considered.Relevant literature was chosen according to the objective of this review. Relevant literature was searched by 3 independent investigators, and experts in the field of miRNAs and psoriasis were involved in analyzing process.We included any study in which role of miRNAs in psoriasis was examined in relation to disease pathogenesis, diagnosis, and treatment.The specific miRNAs profile has been identified from human psoriatic skin, blood, and hair samples. It is found that genetic polymorphisms related to some of specific miRNAs, miR-146a for example, are associated with psoriasis susceptibility. Key roles of several unique miRNAs, such as miR-203 and miR-125b, in inflammatory responses and immune dysfunction, as well as hyperproliferative disorders of psoriatic lesions have been revealed. Moreover, circulating miRNAs detected from blood samples have a potential of clinic application to be the biomarkers of diagnosis, prognosis, and treatment responses. Additionally, a new layer of regulatory mechanisms mediated by miRNAs is to some extent revealed in pathogenesis of psoriasis.The dramatically altered mRNA expression profiles are displayed in psoriasis, and some of these may become disease markers and therapeutic targets. Herein, this work underscores the potential importance of miRNAs to diagnosis, prognosis, and treatment of psoriasis. However, further study in this field is worth doing in the future, as the exact roles of miRNAs in psoriasis have not been fully elucidated.Systematic review registration number is not registered.     

The Role of Gender in Careers in Medicine: a Systematic Review and Thematic Synthesis of Qualitative Literature

AbstractBackgroundGender disparities exist in the careers of women in medicine. This review explores the qualitative literature to understand how gender influences professional trajectories, and identify opportunities for intervention.MethodsA systematic review and thematic synthesis included articles obtained from PubMed, Cochrane Central Register of Controlled Trials (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), and GenderWatch (ProQuest) on June 26 2020, updated on September 10, 2020. Included studies explored specialty choice, leadership roles, practice setting, burnout, promotion, stigma, mentoring, and organizational culture. Studies taking place outside of the USA, using only quantitative data, conducted prior to 2000, or focused on other health professions were excluded. Data were extracted using a standardized extraction tool and assessed for rigor and quality using a 9-item appraisal tool. A three-step process for thematic synthesis was used to generate analytic themes and construct a conceptual model. The study is registered with PROSPERO (CRD42020199999).FindingsAmong 1524 studies identified, 64 were eligible for analysis. Five themes contributed to a conceptual model for the influence of gender on women’s careers in medicine that resembles a developmental socio-ecological model. Gender influences career development externally through culture which valorizes masculine stereotypes and internally shapes women’s integration of personal and professional values.ConclusionMedical culture and structures are implicitly biased against women. Equitable environments in education, mentoring, hiring, promotion, compensation, and support for work-life integration are needed to address gender disparities in medicine. Explicit efforts to create inclusive institutional cultures and policies are essential to support a diverse workforce.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06836-z.KEY WORDS: physician careers, gender, careers in medicine     

The Diagnostic Value of Procalcitonin in Patients with Severe Acute Pancreatitis: A Meta-Analysis

The role of procalcitonin in diagnosing severe acute pancreatitis has not been clearly assessed. This meta-analysis aims to evaluate the overall diagnostic accuracy of procalcitonin as a biomarker for severe acute pancreatitis. Medline (via PubMed), Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, and China WanFang Data were searched systematically for prospective studies reporting procalcitonin as a diagnostic marker of severe acute pancreatitis before August 31, 2021. Sensitivity, specificity, and other measures of the accuracy of procalcitonin in the diagnosis of severe acute pancreatitis were pooled by Stata 15.0 software. Heterogeneity was evaluated by I² test, and the quality of included studies was evaluated by using the Quality Assessment of Diagnostic Accuracy Studies-2 system. Further, the sources of heterogeneity were verified using meta-regression and subgroup analysis, and the publication bias was evaluated by the Deeks’ funnel plot. A total of 18 studies meeting the inclusion criteria were included, containing 1764 patients. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the receiver operating characteristic curve of procalcitonin for diagnosing severe acute pancreatitis were as follows: 0.80 (95% CI: 0.73-0.86), 0.84 (95% CI: 0.78-0.88), 4.95 (95% CI: 3.46-7.09), 0.23 (95% CI: 0.16-0.34), 21.26 (95% CI: 11.09-40.74), 0.89 (95% CI: 0.86-0.92). Also, P > .05 suggested no significant publication bias. Current evidence indicates that procalcitonin has good sensitivity and diagnostic accuracy for severe acute pancreatitis. However, the findings should be carefully used as routine evidence in diagnosing patients with severe acute pancreatitis alone because of the limited number of included studies and high heterogeneity.     

Skin Window Studies of the Acute Inflammatory Responses of Neutropenic Patients

The acute inflammatory responses ofthree cyclic neutropenic and 15 chronicneutropenic patients were studied withthe Rebuck skin window technique.The neutrophil responses at 3 and 5 hrafter initiation of the inflammation wereroughly proportional to the blood neutrophil counts. Cyclic neutropenics intheir neutropenic phase and severechronic neutropenics both showed normal mononuclear cell responses. Theseobservations indicate that neutrophilaccumulation at an inflammatory site isnot necessary to initiate the mononuclearcell response as previously postulated.It is further suggested that in these patients with decreased neutrophils butnormal monocyte counts the monocytesplay a vital role in preventing seriousinfections.

Submitted on March 22, 1971 Accepted on April 5, 1971     

The Therapeutic Use of Analgesics in Patients With Liver Cirrhosis: A Literature Review and Evidence-Based Recommendations

Context:

Pain management in cirrhotic patients is a major clinical challenge for medical professionals. Unfortunately there are no concrete guidelines available regarding the administration of analgesics in patients with liver cirrhosis. In this review we aimed to summarize the available literature and suggest appropriate evidence-based recommendations regarding to administration of these drugs.

Evidence Acquisition:

An indexed MEDLINE search was conducted in July 2014, using keywords “analgesics”, “hepatic impairment”, “cirrhosis”, “acetaminophen or paracetamol”, “NSAIDs or nonsteroidal anti-inflammatory drugs”, “opioid” for the period of 2004 to 2014. All randomized clinical trials, case series, case report and meta-analysis studies with the above mentioned contents were included in review process. In addition, unpublished information from the Food and Drug Administration are included as well.

Results:

Paracetamol is safe in patients with chronic liver disease but a reduced dose of 2-3 g/d is recommended for long-term use. Non-steroidal anti-inflammatory drugs (NSAIDs) are best avoided because of risk of renal impairment, hepatorenal syndrome, and gastrointestinal hemorrhage. Most opioids can have deleterious effects in patients with cirrhosis. They have an increased risk of toxicity and hepatic encephalopathy. They should be administrated with lower and less frequent dosing in these patients and be avoided in patients with a history of encephalopathy or addiction to any substance.

Conclusions:

No evidence-based guidelines exist on the use of analgesics in patients with liver disease and cirrhosis. As a result pain management in these patients generates considerable misconception among health care professionals, leading under-treatment of pain in this population. Providing concrete guidelines toward the administration of these agents will lead to more efficient and safer pain management in this setting.