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Romanian Journal of Internal Medicine =... Sep 2020Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, which requires urgent interventions in order to improve outcomes. Surviving... (Review)
Review
Sepsis is an overwhelming reaction to infection that comes with high morbidity and mortality, which requires urgent interventions in order to improve outcomes. Surviving Sepsis is an international campaign that aims to improve sepsis outcomes. The 2016 guideline modifies the previous definition of sepsis and proposes some specific diagnostic and therapeutic measures, such as the protocolized use of fluid resuscitation and antibiotics. We aim to summarize the main recommendations of the 2016 guideline that are relevant to the internist and evidence-base update them to the year 2020. In the current context, this review doesn't address patients affected by SARS-COV2 induced disease.
Topics: Anti-Bacterial Agents; Biomarkers; Fluid Therapy; Humans; Practice Guidelines as Topic; Sepsis; Vasoconstrictor Agents
PubMed: 32396142
DOI: 10.2478/rjim-2020-0012 -
International Journal of Molecular... Mar 2023(), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The... (Review)
Review
(), the causative agent of TB, is a recalcitrant pathogen that is rife around the world, latently infecting approximately a quarter of the worldwide population. The asymptomatic status of the dormant bacteria escalates to the transmissible, active form when the host's immune system becomes debilitated. The current front-line treatment regimen for drug-sensitive (DS) strains is a 6-month protocol involving four different drugs that requires stringent adherence to avoid relapse and resistance. Poverty, difficulty to access proper treatment, and lack of patient compliance contributed to the emergence of more sinister drug-resistant (DR) strains, which demand a longer duration of treatment with more toxic and more expensive drugs compared to the first-line regimen. Only three new drugs, bedaquiline (BDQ) and the two nitroimidazole derivatives delamanid (DLM) and pretomanid (PMD) were approved in the last decade for treatment of TB-the first anti-TB drugs with novel mode of actions to be introduced to the market in more than 50 years-reflecting the attrition rates in the development and approval of new anti-TB drugs. Herein, we will discuss the pathogenesis, current treatment protocols and challenges to the TB control efforts. This review also aims to highlight several small molecules that have recently been identified as promising preclinical and clinical anti-TB drug candidates that inhibit new protein targets in .
Topics: Humans; Antitubercular Agents; Tuberculosis; Mycobacterium tuberculosis; Drug Delivery Systems; Clinical Protocols; Tuberculosis, Multidrug-Resistant
PubMed: 36982277
DOI: 10.3390/ijms24065202 -
Cleveland Clinic Journal of Medicine Jan 2020Sepsis is a life-threatening organ dysfunction that results from the body's response to infection. It requires prompt recognition, appropriate antibiotics, careful... (Review)
Review
Sepsis is a life-threatening organ dysfunction that results from the body's response to infection. It requires prompt recognition, appropriate antibiotics, careful hemodynamic support, and control of the source of infection. With the trend in management moving away from protocolized care in favor of appropriate usual care, an understanding of sepsis physiology and best practice guidelines is critical.
Topics: Anti-Bacterial Agents; Disease Management; Humans; Practice Guidelines as Topic; Sepsis; Shock, Septic
PubMed: 31990655
DOI: 10.3949/ccjm.87a.18143 -
Indian Journal of Pediatrics Mar 2023Shock in children is associated with significant mortality and morbidity, particularly in resource-limited settings. The principles of management include early... (Review)
Review
Shock in children is associated with significant mortality and morbidity, particularly in resource-limited settings. The principles of management include early recognition, fluid resuscitation, appropriate inotropes, antibiotic therapy in sepsis, supportive therapy for organ dysfunction, and regular hemodynamic monitoring. During the past decade, each step has undergone several changes and evolved as evidence that has been translated into recommendations and practice. There is a paradigm shift from protocolized-based care to personalized management, from liberal strategies to restrictive strategies in terms of fluids, blood transfusion, ventilation, and antibiotics, and from clinical monitoring to multimodal monitoring using bedside technologies. However, uncertainties are still prevailing in terms of the volume of fluids, use of steroids, and use of extracorporeal and newer therapies while managing shock. These changes have been summarized along with evidence in this article with the aim of adopting an evidence-based approach while managing children with shock.
Topics: Child; Humans; Shock, Septic; Sepsis; Shock; Fluid Therapy; Blood Transfusion; Anti-Bacterial Agents; Resuscitation
PubMed: 36715864
DOI: 10.1007/s12098-022-04434-3 -
Journal of Feline Medicine and Surgery Aug 2021The aim of this study was to assess the efficacy and tolerability of lomustine, methotrexate and cytarabine chemotherapy as rescue treatment for feline lymphoma.
OBJECTIVES
The aim of this study was to assess the efficacy and tolerability of lomustine, methotrexate and cytarabine chemotherapy as rescue treatment for feline lymphoma.
METHODS
The medical records of 13 cats treated with lomustine, methotrexate and cytarabine for relapsed high-grade feline lymphoma, at a single institution between 2013 and 2018, were examined. All anatomical types were included. Data were analysed using descriptive statistics.
RESULTS
Nine cats received all three drugs and four cats received only two drugs owing to progressive disease. In cats that received (or in which there was intention to treat with) all three drugs, 6/13 (46%) demonstrated a complete or partial response to chemotherapy. Treatment was generally well tolerated, although two cats experienced Veterinary Comparative Oncology Group (VCOG) grade 3 neutropenia and one cat experienced VCOG grade 3 thrombocytopenia. The median progression-free survival was 61 days (range 16-721 days).
CONCLUSIONS AND RELEVANCE
CHOP-(cyclophosphamide, doxorubicin, vincristine, prednisolone) and COP-based protocols are established first-line chemotherapy for feline lymphoma, but standard rescue protocols are lacking. Lomustine has become a popular single-agent option, but prolonged or cumulative myelosuppression can result in treatment delays, risking relapse. Therefore, a multidrug lomustine-based protocol may be advantageous, and, from first principles, should also better overcome resistance. This study suggests that lomustine, methotrexate and cytarabine may represent an efficacious and well-tolerated protocol for feline lymphoma rescue.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cat Diseases; Cats; Cyclophosphamide; Cytarabine; Lomustine; Lymphoma; Methotrexate; Neoplasm Recurrence, Local
PubMed: 33176543
DOI: 10.1177/1098612X20972066 -
Cancer Science Jul 2021Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys,...
Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)-like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and Y-ibritumomab tiuxetan.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Renal Dialysis; Rituximab; Vincristine; Young Adult
PubMed: 33938097
DOI: 10.1111/cas.14933 -
Current Opinion in Pediatrics Jun 2016Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72 000 children hospitalized for sepsis annually with a reported... (Review)
Review
PURPOSE OF REVIEW
Sepsis is the leading cause of pediatric death worldwide. In the United States alone, there are 72 000 children hospitalized for sepsis annually with a reported mortality rate of 25% and an economic cost estimated to be $4.8 billion. However, it is only recently that the definition and management of pediatric sepsis has been recognized as being distinct from adult sepsis.
RECENT FINDINGS
The definition of pediatric sepsis is currently in a state of evolution, and there is a large disconnect between the clinical and research definitions of sepsis which impacts the application of research findings into clinical practice. Despite this, it is the speed of diagnosis and the timely implementation of current treatment guidelines that has been shown to improve outcomes. However, adherence to treatment guidelines is currently low and it is only through the implementation of protocols that improved care and outcomes have been demonstrated.
SUMMARY
The current management of pediatric sepsis is largely based on adaptations from adult sepsis treatment; however, distinct physiology demands more prospective pediatric trials to tailor management to the pediatric population. Adherence to current and emerging practice guidelines will require that protocolized care pathways become a commonplace.
Topics: Adrenal Cortex Hormones; Anti-Bacterial Agents; Child; Clinical Protocols; Early Diagnosis; Fluid Therapy; Guideline Adherence; Humans; Practice Guidelines as Topic; Sepsis; Time Factors; United States
PubMed: 26983000
DOI: 10.1097/MOP.0000000000000337 -
JAMA Oncology Feb 2018The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to...
Salvage Chemoimmunotherapy With Inotuzumab Ozogamicin Combined With Mini-Hyper-CVD for Patients With Relapsed or Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia: A Phase 2 Clinical Trial.
IMPORTANCE
The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL.
OBJECTIVE
To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL.
DESIGN, SETTING, AND PARTICIPANTS
A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston.
INTERVENTIONS
The chemotherapy used was lower intensity than hyper-CVAD (cyclophosphamide, vincristine, doxorubicin [trade name, Adriamycin; Pfizer], and dexamethasone) and is referred to as mini-hyper-CVD (mini-HCVD: cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine at 0.5 g/m2 × 4 doses). Inotuzumab was given on day 3 of the first 4 courses at 1.8 to 1.3 mg/m2 for cycle 1 followed by 1.3 to 1.0 mg/m2 for subsequent cycles.
MAIN OUTCOMES AND MEASURES
The primary end points were the overall response rate and overall survival (OS). Secondary end points included safety, relapse-free survival (RFS), the rate of allogeneic stem cell transplantation (ASCT), and the minimal residual disease (MRD) negativity rate.
RESULTS
Fifty-nine patients (30 women and 29 men) with a median age of 35 years (range, 18-87 years) were treated. Overall, 46 patients (78%) responded, 35 of them (59%) achieving complete response. The overall MRD negativity rate among responders was 82%. Twenty-six patients (44%) received ASCT. Grade 3 to 4 toxic effects included prolonged thrombocytopenia (81%; n = 48), infections (73%; n = 43), and hyperbilirubinemia (14%; n = 8). Veno-occlusive disease (VOD) occurred in 9 patients (15%). With a median follow-up of 24 months, the median RFS and OS were 8 and 11 months, respectively. The 1-year RFS and OS rates were 40% and 46%, respectively. The 1-year OS rates for patients treated in salvage 1, salvage 2, and salvage 3 or beyond were 57%, 26%, and 39%, respectively (P = .03).
CONCLUSIONS AND RELEVANCE
The combination of inotuzumab with low-intensity mini-HCVD chemotherapy shows encouraging results in R/R ALL. The risk of VOD should be considered carefully in patients with previous liver damage and among transplant candidates.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT01371630.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dacarbazine; Dexamethasone; Dose-Response Relationship, Drug; Doxorubicin; Drug Resistance, Neoplasm; Female; Hematopoietic Stem Cell Transplantation; Humans; Inotuzumab Ozogamicin; Male; Middle Aged; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence; Salvage Therapy; Survival Analysis; Vincristine; Young Adult
PubMed: 28859185
DOI: 10.1001/jamaoncol.2017.2380 -
Frontiers in Pediatrics 2021The implementation of managed protocols contributes to a systematized approach to the patient and continuous evaluation of results, focusing on improving clinical... (Review)
Review
The implementation of managed protocols contributes to a systematized approach to the patient and continuous evaluation of results, focusing on improving clinical practice, early diagnosis, treatment, and outcomes. Advantages to the adoption of a pediatric sepsis recognition and treatment protocol include: a reduction in time to start fluid and antibiotic administration, decreased kidney dysfunction and organ dysfunction, reduction in length of stay, and even a decrease on mortality. Barriers are: absence of a written protocol, parental knowledge, early diagnosis by healthcare professionals, venous access, availability of antimicrobials and vasoactive drugs, conditions of work, engagement of healthcare professionals. There are challenges in low-middle-income countries (LMIC). The causes of sepsis and resources differ from high-income countries. Viral agent such as dengue, malaria are common in LMIC and initial approach differ from bacterial infections. Some authors found increased or no impact in mortality or increased length of stay associated with the implementation of the SCC sepsis bundle which reinforces the importance of adapting it to most frequent diseases, disposable resources, and characteristics of healthcare professionals. Conclusions: (1) be simple; (2) be precise; (3) education; (5) improve communication; (5) work as a team; (6) share and celebrate results.
PubMed: 34858905
DOI: 10.3389/fped.2021.755484 -
Seminars in Oncology Oct 2015During the past decade, biomedical technologies have undergone an explosive evolution-from the publication of the first complete human genome in 2003, after more than a... (Review)
Review
During the past decade, biomedical technologies have undergone an explosive evolution-from the publication of the first complete human genome in 2003, after more than a decade of effort and at a cost of hundreds of millions of dollars-to the present time, where a complete genomic sequence can be available in less than a day and at a small fraction of the cost of the original sequence. The widespread availability of next-generation genomic sequencing has opened the door to the development of precision oncology. The need to test multiple new targeted agents both alone and in combination with other targeted therapies, as well as classic cytotoxic agents, demands the development of novel therapeutic platforms (particularly Master Protocols) capable of efficiently and effectively testing multiple targeted agents or targeted therapeutic strategies in relatively small patient subpopulations. Here, we describe the Master Protocol concept, with a focus on the expected gains and complexities of the use of this design. An overview of Master Protocols currently active or in development is provided along with a more extensive discussion of the Lung Master Protocol (Lung-MAP study).
Topics: Clinical Protocols; Clinical Trials as Topic; Genetic Testing; Genomics; High-Throughput Nucleotide Sequencing; Humans; Lung Neoplasms; Molecular Targeted Therapy; Neoplasms; Precision Medicine; Research Design; Sequence Analysis, DNA
PubMed: 26433553
DOI: 10.1053/j.seminoncol.2015.07.009