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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 -
Biomedicine & Pharmacotherapy =... Sep 2020The growing number of concussions and mild traumatic brain injuries (mTBI) with the lack of evidence-based treatment options is a continuous health concern. This creates... (Review)
Review
The growing number of concussions and mild traumatic brain injuries (mTBI) with the lack of evidence-based treatment options is a continuous health concern. This creates problems when evaluating and providing efficacious symptom management to patients suffering from post-concussion syndrome (PCS). Numerous pharmacological and non-pharmacological agents have been utilized in an attempt to treat PCS. Some of these approaches include physical therapy, analgesics, antidepressants, and nutraceuticals. Although these treatments have had some success, there has been inconsistent outcomes, with some examples of patients' symptoms worsening. Among pharmaceutical agents, fluoxetine has been a popular choice for the symptom management of PCS. Although some patients have had symptom resolution with the use of fluoxetine, there is still a lack of conclusive data. Of the several biochemical changes that occur in a patient's brain following a concussion, an increase in reactive oxygen species (ROS) is of particular concern. In order to counteract the responses of the brain, antioxidants, such as ascorbic acid, have been utilized to reverse the damaging cellular effects. However, this may inadvertently cause an increase in ROS, rather than a reduction. Although there is a lack of consistency in exactly when each treatment was used in the post-injury interval, it is important that we analyze the strengths and weaknesses of the most commonly used agents due to the lack of a set protocol. The studies were chosen in a non-exhaustive manner and were not consistent in patients' post-injury intervals, in addition to other baseline characteristics. However, over-arching claims that some treatments may benefit more than others can be made. This review evaluates both the pharmaceutical and non-pharmaceutical protocols that are most commonly utilized in post-concussive patients for their efficacy in treatment of post-concussive syndrome (PCS).
Topics: Brain; Brain Concussion; Clinical Protocols; Evidence-Based Medicine; Humans; Post-Concussion Syndrome; Treatment Outcome
PubMed: 32768934
DOI: 10.1016/j.biopha.2020.110406 -
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 -
American Journal of Obstetrics and... Aug 2019To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols.
DATA SOURCES
PubMed, Embase, and the Cochrane library searched up to July 2018.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared women with ectopic pregnancies receiving the single-dose, two-dose, or multi-dose methotrexate protocols.
STUDY APPRAISAL AND SYNTHESIS METHODS
Odds of treatment success, treatment failure, side effects, and surgery for tubal rupture, as well as length of follow-up until treatment success, were compared using random and fixed effects meta-analysis. Sensitivity analyses compared treatment success in the groups with high human chorionic gonadatropin (hCG) values and a large adnexal mass, as defined by individual studies. The Cochrane Collaboration tool was used to assess risk of bias.
RESULTS
The 2-dose protocol was associated with higher treatment success compared to the single-dose protocol (odds ratio [OR], 1.84; 95% CI, 1.13, 3.00). The 2-dose protocol was more successful in women with high hCG (OR, 3.23; 95% CI, 1.53, 6.84) and in women with a large adnexal mass (OR, 2.93; 95% CI, 1.23, 6.9). The odds of surgery for tubal rupture were lower in the 2-dose protocol (OR, 0.65; 95% CI, 0.26, 1.63), but this was not statistically significant. The length of follow-up was 7.9 days shorter for the 2-dose protocol (95% CI, -12.2, -3.5). The odds of side effects were higher in the 2-dose protocol (OR, 1.53; 95% CI, 1.01, 2.30). Compared to the single-dose protocol, the multi-dose protocol was associated with a nonsignificant reduction in treatment failure (OR, 0.56; 95% CI, 0.28, 1.13) and a higher chance of side effects (OR, 2.10; 95% CI, 1.24, 3.54). The odds of surgery for tubal rupture (OR, 1.62; 95% CI, 0.41, 6.49) and time to follow-up (OR, -1.3; 95% CI, -5.4, 2.7) were similar.
CONCLUSION
The 2-dose methotrexate protocol is superior to the single-dose protocol for the treatment of ectopic pregnancy in terms of treatment success and time to success. Importantly, these findings hold true in patients thought to be at a lower likelihood of responding to medical management, such as those with higher hCGs and a large adnexal mass.
Topics: Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Fallopian Tubes; Female; Humans; Methotrexate; Pregnancy; Pregnancy, Ectopic; Randomized Controlled Trials as Topic; Rupture
PubMed: 30629908
DOI: 10.1016/j.ajog.2019.01.002 -
BMC Cancer Mar 2021Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer...
Total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine for resectable and borderline resectable pancreatic cancer (PREOPANC-2 trial): study protocol for a nationwide multicenter randomized controlled trial.
BACKGROUND
Neoadjuvant therapy has several potential advantages over upfront surgery in patients with localized pancreatic cancer; more patients receive systemic treatment, fewer patients undergo futile surgery, and R0 resection rates are higher, thereby possibly improving overall survival (OS). Two recent randomized trials have suggested benefit of neoadjuvant chemoradiotherapy over upfront surgery, both including single-agent chemotherapy regimens. Potentially, the multi-agent FOLFIRINOX regimen (5-fluorouracil with leucovorin, irinotecan, and oxaliplatin) may further improve outcomes in the neoadjuvant setting for localized pancreatic cancer, but randomized studies are needed. The PREOPANC-2 trial investigates whether neoadjuvant FOLFIRINOX improves OS compared with neoadjuvant gemcitabine-based chemoradiotherapy and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer patients.
METHODS
This nationwide multicenter phase III randomized controlled trial includes patients with pathologically confirmed resectable and borderline resectable pancreatic cancer with a WHO performance score of 0 or 1. Resectable pancreatic cancer is defined as no arterial and ≤ 90 degrees venous involvement; borderline resectable pancreatic cancer is defined as ≤90 degrees arterial and ≤ 270 degrees venous involvement without occlusion. Patients receive 8 cycles of neoadjuvant FOLFIRINOX chemotherapy followed by surgery without adjuvant treatment (arm A), or 3 cycles of neoadjuvant gemcitabine with hypofractionated radiotherapy (36 Gy in 15 fractions) during the second cycle, followed by surgery and 4 cycles of adjuvant gemcitabine (arm B). The primary endpoint is OS by intention-to-treat. Secondary endpoints include progression-free survival, quality of life, resection rate, and R0 resection rate. To detect a hazard ratio of 0.70 with 80% power, 252 events are needed. The number of events is expected to be reached after inclusion of 368 eligible patients assuming an accrual period of 3 years and 1.5 years follow-up.
DISCUSSION
The PREOPANC-2 trial directly compares two neoadjuvant regimens for patients with resectable and borderline resectable pancreatic cancer. Our study will provide evidence on the neoadjuvant treatment of choice for patients with resectable and borderline resectable pancreatic cancer.
TRIAL REGISTRATION
Primary registry and trial identifying number: EudraCT: 2017-002036-17 . Date of registration: March 6, 2018. Secondary identifying numbers: The Netherlands National Trial Register - NL7094 , NL61961.078.17, MEC-2018-004.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Deoxycytidine; Fluorouracil; Gemcitabine; Irinotecan; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Clinical Trials, Phase III as Topic
PubMed: 33757440
DOI: 10.1186/s12885-021-08031-z -
Blood Mar 2020Administering asparaginase has always been problematic in adults because most general oncologists who treat adults are not familiar with its usage and toxicity. The... (Review)
Review
Administering asparaginase has always been problematic in adults because most general oncologists who treat adults are not familiar with its usage and toxicity. The toxicity profile of the drug is unique and is not observed with any other chemotherapy agent. Furthermore, asparaginase is almost exclusively used in acute lymphoblastic leukemia (ALL), which is a very rare cancer in adults. Currently, the long-acting pegylated form (pegasparaginase) is the only Escherichia coli-derived asparaginase available in the United States. The use of pediatric regimens is likely to lead to more adult patients receiving multiple doses of pegasparaginase. However, oncologists who treat adults may be reluctant to use pegasparaginase or may unnecessarily discontinue administering it because of certain adverse effects. As a result, the clinical benefit of multiple doses of pegasparaginase will be missed. Despite the fact that pegasparaginase is associated with unique toxicities, the majority are nonfatal, manageable, and reversible. Here, we describe real-life cases of adults with ALL who were treated with pediatric-inspired regimens that incorporated pegasparaginase to illustrate the management of several pegasparaginase-associated adverse effects and guide whether and how to continue the drug.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asparaginase; Drug-Related Side Effects and Adverse Reactions; Humans; Polyethylene Glycols; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 31977001
DOI: 10.1182/blood.2019002477 -
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