Inadequate Therapy Research Articles

Multimodality cardiovascular imaging in pulmonary embolism

Acute pulmonary embolism (APE) is one of the leading causes of cardiovascular (CV) morbidity and mortality. To select appropriate therapeutic strategy and/or to minimize the mortality and morbidity, rapid and correct identification of life-threatening APE is very important. Also, right ventricular (RV) failure usually precedes acute hemodynamic compromise or death, and thus the identification of RV failure is another important step in risk stratification or treatment of APE. With advances in diagnosis and treatment, the prognosis of APE has been dramatically improving in most cases, but inadequate therapy or recurrent episodes of pulmonary embolism (PE) may result in negative outcomes or, so called, chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is a condition characterized by remaining chronic thromboembolic material in the pulmonary vasculature and subsequent chronic pulmonary hypertension. Various imaging modalities include chest computed tomography pulmonary angiography (CTPA), echocardiography, magnetic resonance imaging, and nuclear imaging and each are used for the assessment of varying status of PE. Assessment of thromboembolic burden by chest CTPA is the first step in the diagnosis of PE. Hemodynamic assessment can be achieved by echocardiography and also by chest CTPA. Nuclear imaging is useful in discriminating CTEPH from APE. Better perspectives on diagnosis, risk stratification and decision making in PE can be provided by combining multimodality CV imaging. Here, the advantages or pitfalls of each imaging modality in diagnosis, risk stratification, or management of PE will be discussed.

Does thoracic epidural anaesthesia constitute over-instrumentation in video- and robotic-assisted thoracoscopic lung parenchyma resections?

Effective and sustained perioperative analgesia in thoracic surgery and pulmonary resection is beneficial to patients by reducing both postoperative pulmonary complications and the incidence of chronic pain. In this review, the indication of thoracic epidural anaesthesia in video- (VATS) and robotic-assisted (RATS) thoracoscopy shall be critically objectified and presented in a differentiated way. Pain following VATS and RATS has a negative influence on lung function by inhibiting deep respiration, suppressing coughing and secretion and favours the development of atelectasis, pneumonia and other postoperative pulmonary complications.In addition, inadequate pain therapy after these procedures may lead to chronic pain. Since clear evidence-based recommendations for optimal postoperative analgesia are still lacking in VATS and RATS, there can be no universal recommendation that fits all centres and patients. In this context, thoracic epidural analgesia is the most effective analgesia procedure for perioperative pain control in VATS and RATS-assisted surgery for patients with pulmonary risk factors.

Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment.

Simple SummaryAround 4% of cancer deaths in the world was associated to ovarian cancer (OC), making it the eighth most common cause of death in women. Increasing evidence suggests that ion channels play critical role in the main stages of OC process, including proliferation, migration and metastasis. The aim of this review was to provide an updated description of the current knowledge concerning ion channels’ involvement in OC, with a particular emphasis of their role in the acquired chemoresistance. Importantly, ion channels might represent new molecular targets for the development of OC treatment, exploiting the availability of the well-known ion channel-targeting drugs.Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

Характеристика BRCA-ассоциированного рака молочной железы в российской популяции

"Standard" diagnostic panels allow identification of only a few of BRCA1 and BRCA2 gene mutations most common in a population. Therefore, tests relying on such panels may return false negative results, since the coding regions of these genes may have other defects. For breast cancer (BC) patients, false negative test results may translate into selection of inadequate therapy by their doctors. This study aimed to identify the features of BRCA-associated breast cancer in the population of the Russian Federation. The study included breast cancer patients (n = 4440). At the first stage, all patients were screened for the eight most common BRCA1 and BRCA2 genes mutations with the help of real-time PCR. Next, patients that exhibited clinical signs of a hereditary disease (CSHD) in the absence of common mutations (n = 290) had the entire coding regions of BRCA1 and BRCA2 genes studied with next generation sequencing (NGS). "Standard" mutations in the BRCA1 and BRCA2 genes were identified in 169 (3.8%) cases. In the CSHD group, such mutations were revealed in 15.4% of cases. NGS uncovered 33 rare pathogenic BRCA1 and BRCA2 gene mutations in 40 out of 290 breast cancer patients (13.8%). It was concluded that among the residents of the Russian Federation, the range of pathogenic variants of BRCA-associated breast cancer is wide, and it stretches beyond the mutations considered by the "standard" diagnostic panels. Analysis of the entire coding regions of BRCA1 and BRCA2 genes allows increasing efficiency of detection of germline mutations in breast cancer patients at least twofold.

Recent advances in phytochemical-based Nano-formulation for drug-resistant Cancer

The graph of drug resistance in cancer is reportedly increasing in terms of therapeutic efficiency. As per the WHO reports, around 70% of death reported in low- and middle-income countries. The increase in death toll was imparted from improper diagnosis and inadequate therapy. The 25% increase in disease burden may be laden due to resistance mutations in cancer during treatment. Exposure of high concentrations of chemotherapeutic agents leads to toxicity in the normal cells. Long-term conventional chemotherapy develops acquired resistance. The conventional therapeutics was not able to target the cancer cell specifically and need to promulgate the use of nanocarrier or bioengineering for the polychemotherapy. Phytochemicals are natural constituents providing alternative therapeutic approach to minimize the resistance. The present review highlights the nano-therapeutic approaches pondering over the conventional chemotherapy. The phytochemicals are extracted, isolated, and purified from daily dietary fibers or natural plants. Natural extractives act via multiple pathways and provide optimum effectiveness against resistance cancer. The poor solubility and bioavailability are major constraints in combination therapy. The nanotechnological approach improves the functional properties transportation across cell barriers, and improves bioavailability. The present review highlights the phytochemical based nanoformulations in improving the therapeutic response and several alternative ways to target resistance cancer. The major implications of phytochemical and chemotherapeutic combination therapy could lead in the future.

Resistant Tuberculosis: the Latest Advancements of Second-line Antibiotic Inhalation Products.

Drug-resistant tuberculosis (TB) can be considered the man-made result of interrupted, erratic or inadequate TB therapy. As reported in WHO data, resistant Mycobacterium tuberculosis (Mtb) strains continue to constitute a public health crisis. Mtb is naturally able to survive host defence mechanisms and to resist most antibiotics currently available. Prolonged treatment regimens using the available first-line drugs give rise to poor patient compliance and a rapid evolution of strains resistant to rifampicin only or to both rifampicin and isoniazid (multi drug-resistant, MDR-TB). The accumulation of mutations may give rise to extensively drug-resistant strains (XDR-TB), i.e. strains with resistance also to fluoroquinolones and to the injectable aminoglycoside, which represent the second-line drugs. Direct lung delivery of anti-tubercular drugs, as an adjunct to conventional routes, provides high concentrations within the lungs, which are the intended target site of drug delivery, representing an interesting strategy to prevent or reduce the development of drug-resistant strains. The purpose of this paper is to describe and critically analyse the most recent and advanced results in the formulation development of WHO second-line drug inhalation products, with particular focus on dry powder formulation. Although some of these formulations have been developed for other lung infectious diseases (Pseudomonas aeruginosa, nontuberculous mycobacteria), they could be valuable to treat MDR-TB and XDR-TB.

Calcium and Vitamin D Supplementation in Osteoporosis and Fragility Hip Fracture Patients: A Retrospective NHANES Study

AbstractAdequate vitamin D and calcium supplementation therapy in osteoporosis reduces the risk of fragility fractures and correlates with improved mortality outcomes in postoperative fragility hip fracture patients. However, the prevalence of adequate supplementation in this population remains unclear. Our purpose was to describe supplement use among the adult population in United States who have been told they had osteoporosis and identify factors associated with adequate supplementation, particularly in patients with history of hip fracture. The study sample comprised a total of 15,968 respondents from the National Health and Examinations Survey (NHANES 2007–2010, 2013–2014); 1,065 self-reported a diagnosis of osteoporosis and 266 self-reported a history of hip fracture. Additional patient factors were analyzed by multivariable logistic regression to assess associated factors of adequate vitamin D (≥ 600 international unit [IU]/day) and calcium (≥ 1000 mg/day) supplementation. The prevalence of vitamin D and calcium supplementation was significantly higher in the osteoporosis group than without (p = 0.001). However, supplemental intake reached adequate levels (≥ 600 IU/day of vitamin D and ≥ 1000mg/day of calcium) in only 28.8% of individuals with osteoporosis for vitamin D, 51.6% for calcium, and 19.2% for both. Of individuals with additional history of hip fracture, only 14% reported adequate intake of both nutrients. Female sex (odds ratio [OR]: 2.35, p < 0.001), older age (OR: 1.02, p < 0.001), and Caucasian race (OR: 1.456, p = 0.004) were positive factors of adequate supplementation, while Hispanic ethnicity was a negative factor (OR: 0.658, p = 0.009). Unexpectedly, a history of hip fracture did not affect the odds of adequate treatment (OR: 0.685, p = 0.176). Adults with known osteoporosis in the United States are self-reporting inadequate supplementation therapy, and significant gender and racial disparities exist. There is a broad need for improved supplementation to help manage this disease, particularly among adults with prior hip fracture, a vulnerable population most relevant for orthopaedic surgeons. This study serves as a call-to-action for orthopaedic surgeons to ensure their fragility hip fracture patients receive adequate supplementation postoperatively to maximize their health and recovery. This was a Level III, retrospective cohort study.

Mother-to-Child HIV Transmission among Pregnant Women in a City with the Highest Rates of HIV in Brazil.

Most of the HIV pediatric infections are acquired through mother-to-child transmission (MTCT). Porto Alegre is a state capital of Brazil that had a HIV MTCT rate of 4.1% in 2013 and the highest rate of HIV-infected pregnant women in the country during 2018. Zidovudine and nevirapine have been used in Brazil for high-risk newborns since 2012. The aim of the study was to investigate HIV MTCT rate and the factors associated with HIV transmission at a hospital that is a reference center for HIV-infected mothers in Porto Alegre, after the introduction of this policy. This retrospective cohort study included all HIV-exposed infants born between February 2013 and December 2016 at the Hospital de Clínicas de Porto Alegre. Student's t-test or Fisher's exact test was used to compare variables between HIV-infected and uninfected groups of newborns. Poisson's regression with robust variance was used to determine the factors associated with HIV MTCT. A total of 375 newborns were exposed to HIV, with an outpatient loss of 14.4% (n = 54). The HIV MTCT rate was 2.18% (n = 7), with four infected during the intrauterine period. The risk factors for MTCT were no prenatal care (relative risk [RR] = 9.4; 95% confidence interval [CI]: 2.0-44.3), late maternal HIV diagnosis in the peripartum period (RR = 16.3; 95% CI: 3.6-73.0), syphilis infection during pregnancy (RR = 9.3; 95% CI: 2.1-40.3), maternal viral load >1,000 copies/mL in the third trimester or peripartum period (RR = 9.5; 95% CI: 1.7-50.5), and lack of or inappropriate antiretroviral therapy during pregnancy (RR = 8.2; 95% CI: 1.6-41.4). MTCT rate was 2.18%. With the institution of two-drug prophylaxis for high-risk newborns, persistent cases HIV MTCT were predominantly found among women with absence of antenatal care, late HIV diagnosis, syphilis coinfection, high viral load, and inadequate ARV therapy during pregnancy. Although zidovudine and nevirapine were administered postnatally to high-risk newborns, this regimen could not prevent transplacental transmission. · Most of the HIV pediatric infections are acquired through mother-to-child transmission.. · The study investigated HIV MTCT rate and the factors associated with HIV transmission in Brazil.. · HIV MTCT rate was 2.18% and most of them were infected during the intrauterine period..

Trauma and Antimicrobial Resistance Are Independent Predictors of Inadequate Empirical Antimicrobial Treatment of Ventilator-Associated Pneumonia in Critically Ill Patients.

Background: We aimed to assess independent risk factors for inadequate initial antimicrobial treatment (IAT) in critically ill patients with ventilator-associated pneumonia (VAP) treated in intensive care units (ICU) and to determine whether IAT is associated with adverse outcomes in patients with VAP. Patients and Methods: A prospective cohort study was performed and included 152 patients with VAP treated in an ICU for more than 48 hours. The main outcomes of interest were all-cause ICU mortality and VAP-related mortality. Other outcomes considered were: intra-hospital mortality, VAP-related sepsis, relapse, re-infection, length of stay in ICU (ICU LOS), and number of days on mechanical ventilation (MV). Results: One-third of patients (35.5%) received inadequate antimicrobial therapy. Trauma (odds ratio [OR], 3.55; 95% confidence interval [CI], 1.25-10.06) and extensively drug-resistant (XDR) causative agent (OR, 3.09; 95% CI, 1.23-7.74) were independently associated with inadequate IAT. Inadequate IAT was associated with a higher mortality rate (OR, 3.08; 95% CI, 1.30-7.26), VAP-related sepsis (OR, 2.39; 95% CI, 1.07-5.32), relapse (OR, 3.25; 95% CI, 1.34-7.89), re-infection (OR, 6.06; 95% CI, 2.48-14.77), and ICU LOS (β 4.65; 95% CI, 0.93-8.36). Acinetobacter spp., Pseudomonas aeruginosa and Klebsiella/Enterobacter spp. were the most common bacteria in patients with IAT and those with adequate antimicrobial therapy. Conclusions: This study demonstrated that inadequate IAT is associated with a higher risk of the majority of adverse outcomes in patients with VAP treated in ICUs. Trauma and XDR strains of bacteria are independent predictors of inadequate IAT of VAP in critically ill patients.

Factores de riesgo en artroplastia total y parcial de cadera: infección y mortalidad

BackgroundSurveillance systems make it possible to analyze the trends of infections associated with hip arthroplasty. The aim of this study is to determine risk factors associated with surgical site infection (SSI) and mortality following total hip arthroplasty (THA) or hemiarthroplasty (HHA). MethodsObservational study including individuals ≥18years who underwent THA or HHA between January 2007 and December 2017. Incidences of SSI were compared with the national rates according to NNIS indexes. Risk factors for SSI and mortality were evaluated using multiple logistic regression model. ResultsIn THA, an association with a higher risk of SSI was found with Hospital Stay (OR 1.08; 95%CI: 1.02-1.15; P=.007).In HHA, hospital stay was associated with a higher risk of SSI (OR 1.05; 95%CI: 1.02-1.08, P=.001), as also happened with obesity (OR 13.28; 95%CI: 2.68-65.74; P=.002), while inadequate antibiotic prophylaxis was associated with a higher risk of mortality (OR 4,69; 95%CI: 1.01-21.74; P=.048) ConclusionIn THA, hospital stay was associated with an increased risk of SSI. In HHA this association is found with hospital stay and obesity, while inadequate antibiotic therapy was associated with mortality.

Hubungan Drug Related Problems (DRPs) Obat Antidiabetika terhadap Ketercapaian Kendali Glikemik pada Pasien Rawat Inap Diabetes Melitus Tipe 2 dengan Komplikasi Nyeri Neuropati

Drug Related Problems (DRPs) associated with Type-2 Diabetes Melitus is commonly caused by multi drug prescription since Type-2 Diabetes Mellitus has comorbid dan complication diseases. Neuropathic pain has 50% prevalence of Type-2 diabetes Mellitus Complication. DRPs can cause can cause inadequate therapy that might be the risk factor leads to neuropathic pain. This study was aimed to investigate the association between drug related problems of antidiabetic medication with glicemic control of hospitalized type 2 diabetes melitus with neuropathic pain patients. Cohort-study is used in this study. 50 patients were conducted in this study that underwent Hospital treatment at Rumah Sakit Akademik Universitas Gadjah Mada during the periods of 2018-2019. This study involved 50 patients who were divided into groups that experienced DRPs by 36 patients and non DRPs by 14 patients. All of the 50 has meet the inclusions criterias. Statistical analysis was using Chi-square test 95% confidence interval (p < 0.05). A number of 38 DRPs have found consists of 26,3% need more therapy, 55,2% with wrong drug therapy, 18,4% inadequate dosing. There was an association between DRPs of antidiabetics regiments and glycemic target on Type-2 Diabetes Mellitus patients with neuropathic pain complication (p=0,005). Identification of DRPs is needed to prevent the negative effect of patient therapy outcomes.

Fluid Responsiveness in the Critically Ill Patient.

Accurate assessment of intravascular volume status in critically ill patients remains a very challenging task. Recent data have shown adverse outcomes in critically ill patients with either inadequate or overaggressive fluid therapy. Understanding the tools and techniques available for accurate volume assessment is imperative. This article discusses the concept of fluid responsiveness and reviews methods for assessing fluid responsiveness in critically ill patients.

Nosocomial infections: Importance of rapid and early detection of ESBL Enterobacteriaceae by molecular biology

Nosocomial infections are a major public health problem. They are mainly caused by bacteria that often present antibiotic resistance profiles, which complicates their management. The diagnosis of these infections is based on clinical and biological criteria that lack sensitivity and specificity, and on microbiological examinations that are lengthy. Unfortunately, the inadequate empirical antibiotic therapy in many cases, and the late implementation of an effective treatment, are associated with the emergence and spread of bacteria that are multi-resistant to antibiotics, i.e. strains producing extended-spectrum beta-lactamases (ESBL). Rapid diagnostic methods, identifying the pathogen and its resistance profile, are therefore necessary. Our laboratory is committed to develop PCR techniques to genotypically identify the most frequent ESBLs from four hospital facilities. Among all the enterobacteria detected, we observed the predominance of OXA type ESBL (38%), followed by CTX-M type ESBL (33%). TEM and SHV genes represent respectively 19% and 10%.The optimization of these technologies could allow the identification of all known resistance mechanisms in only a few hours and find new preventive or curative strategies in the fight against these nosocomial infections, to better respond to this health threat.

A real world investigation on prevalence, clinical features, and therapy of inflammatory bowel disease in the city of Messina, Italy.

Background:The absence of a national register of inflammatory bowel diseases (IBD) hinders effective health care planning in Italy.Aims:to investigate prevalence of IBD in the city of Messina, Italy, based on General Practitioner (GP) records, and to establish current treatments prescribed by different health care providers.Methods:data were extracted from GP databases with the help of disease-specific healthcare cost exemption codes combined with ICD9 codes for ulcerative colitis (UC) and Crohn’s disease (CD), and prescription for mesalazine. Disease and treatment-related data were collected together with information on employment status and the current healthcare provider.Results:Eighty-six GPs participated covering a population of 100,834 people. IBD prevalence (419/105) was 80% higher than estimates of the Regional Health Authorities. Incidence showed a seven-fold increase over the past 30 years. Only 51% of CD and 26% of UC patients were followed by a dedicated IBD centre with more frequent prescriptions of immunomodulators and biologics (p<0.001) compared to GPs.Conclusions:Real world data show much higher figures on IBD prevalence than administrative estimates. Differences in therapeutic approaches between IBD-specialists and non-specialists may reflect poor confidence in managing immunosuppressive therapies by the latter, but may lead to inadequate therapy and cancer surveillance.

The capacity and effectiveness elimination domestic animals allergens: myths and realities

At present, sensitization to airborne allergens in domestic animals is absolutely rightly considered one of the key risk factors for the development of allergic rhinitis and bronchial asthma, as well as largely determines the development of severe forms of atopic dermatitis and respiratory allergosis. Of particular importance is the fact that, unlike other triggers, the elimination of allergens in domestic animals is often associated with internal resistance from patients. Various aspects of this problem are associated with a large number of baseless statement that lead to inadequate prevention and therapy, as well as negatively affecting the social activity of patients and their families. The article presents the current data on the prevalence of sensitization, the properties and clinical significance of the allergens of domestic animals, outlines approaches to conducting elimination activities.

Clinical and economical improvements after introducing rapid identification of bacteria and early antibiotic susceptibility testing in sepsis and bloodstream infections. Results of the PHENOMENON study.

Background: Sepsis and bloodstream infections pose severe challenges in intensive care. Early reliable diagnosis is the key to successful therapy. The objective of the study presented here was to investigate the clinical and economical effects of the new PhenoTM BC test, which allows bacteria identification (ID) and antimicrobial susceptibility testing (AST) in approximately 7 hours after a blood culture becomes positive (BC+).Methods: Historically controlled interventional study. Population: patients with BC+ and ICU admission. Inadequate initial antimicrobial therapy (IAT) is need of therapy change based on result. Prospectively the new test was used in addition. Primary endpoint: time-to-result in hours. Contribution margin (CM) i.e. revenue – costs was computed. All patients formed the intention-to-treat population (ITT). Patients with complete cost data formed the modified ITT group (mITT). CM results were calculated for mITT and PP. Further analyses: length-of-stay (LOS) and mortality.Results: 223 historical and 200 prospective patients were included. Time to result (ITT) was shortened by 51.1 hours (83 vs. 31.9; p<0.001). Overall savings (mITT) were 257,100 € (–301,264 € vs. –44,164 €). 143 of 181 (79%) patients had a test performed, 126 of 143 (88%) having a clinically useable result. 40 (32%) had IAT vs. 65 (29%) in the historic cohort. Median time to AST in PP was shortened by 61.7 hours (89.5 vs. 27.8; p<0.001). LOS was shortened 7 days (28 vs. 19; p=0.226) and mortality was 8% (40.5% vs. 32.5%; p=0.440) lower. Median CM +3,074.80 € per case (–2,350.50 € vs. +724.70 €; p=0.040). Conclusion: The new PhenoTM ID+AST test leads to faster and clinically meaningful results and saves money by shortening LOS on the ICU.

Disorders of carbohydrate metabolism in critical conditions

Background. Carbohydrate metabolism disorders (CMD) include ketoacidosis and ketoacidotic hyperglycemic coma, non-diabetic ketoacidosis, hyperosmolar coma, hypoglycemic syndrome and hypoglycemic coma, lactic acid coma. The main factors in the development of CMD are newly diagnosed diabetes mellitus (DM) or inadequate therapy of previously diagnosed DM, infectious processes, acute diseases (myocardial infarction, strokes, pancreatitis, renal failure, severe burns, thyrotoxicosis), use of certain drugs (calcium channel blockers, osmotic and thiazide diuretics, propranolol, chemotherapeutic drugs), alcohol or cocaine abuse.&#x0D; Objective. To describe the course and management of patients with CMD.&#x0D; Materials and methods. Review of the available literature on this issue.&#x0D; Results and discussion. CMD in critical conditions leads to the development of hyperglycemia, hyperketonemia, metabolic acidosis, dehydration, hyperosmolarity, electrolyte imbalance, arising against the background of the underlying disease, being masked by it and worsening the patient’s condition. When diagnosing ketoacidosis, one should focus primarily on the clinical condition of the patient, because the test for ketonuria does not reflect the actual level of ketone bodies in the urine. CMD therapy should include rehydration (infusion therapy – IT), insulin therapy, partial correction of severe metabolic acidosis, use of antiketogenic drugs, compensation of electrolyte disorders and elimination of the CMD causes. Isotonic NaCl solution or Ringer solution must be used for IT. Elderly patients and patients with heart failure should be treated with caution, with a possible dose reduction of 50 %. In case of hyperglycemia, insulin therapy (intravenous bolus 0.15 IU/kg, then infusion 0.1 IU/kg/h) is prescribed to ensure a reduction in glucose concentration by 2-3 mmol/L per hour. To correct metabolic acidosis, hydrocarbonate solutions are prescribed under the control of acid-base status (ABS). If it is not possible to determine ABS, in the presence of clinical signs of ketoacidosis, it is possible to prescribe Soda-Bufer (“Yuria-Pharm”) up to 300 ml. Xylitol (Xylate, “Yuria-Pharm”) is the main antiketogenic solution. It reduces the amount of free fatty acids, which oxidize to acetyl-CoA, acts as an insulin-independent energy source, increases the intensity of glycolysis and glycogen production, stimulates insulin secretion. If the patient has a fasting blood glucose level &gt;13.9 mmol/L, nausea, vomiting, dizziness, drowsiness, dry skin and dry mouth, Kussmaul’s breathing, frequent urination, or a patient with diabetes is scheduled for surgery, it is advisable to prescribe xylitol-containing solution. Xylate should be prescribed for various CMD (hyperglycemia, dehydration, hypokalemia, ketoacidosis). Another area of CMD treatment is the normalization of potassium levels, which should be started in the conditions of normokalemia, because CMD are characterized by an initial increase and subsequent decrease in potassium content. The latter should be maintained at 4-5 mmol/h with tight monitoring every 2 hours firstly and then every 4 hours.&#x0D; Conclusions. 1. Many patients in the intensive care unit develop CMD. 2. CMD in critical conditions involve the development of hyperglycemia, hyperketonemia, metabolic acidosis, dehydration, hyperosmolarity, and electrolyte imbalance. 3. CMD therapy should include rehydration, insulin therapy, partial correction of severe metabolic acidosis, use of antiketogenic drugs, compensation of electrolyte disorders and elimination of the CMD causes. 4. Isotonic NaCl solution, Ringer solution, insulin therapy, hydrocarbonate solutions, xylitol, potassium preparations are used in CMD therapy.

MODERN APPROACHES IN MANAGING WOUND DEFECTS IN CHILDREN WITH SURGICAL INFECTION

The results of treatment of 57 children with wound defects of soft tissues that have appeared at the background of surgical infections of various origins have been analyzed. The causes of the wound defects formation were analyzed according to the T.I.M.E. system.[7,8,9]. While treating the wound defects the strategy of creating the conditions close to the ones in an acute wound was followed («Wound bed preparation») [7,8,11]. We used several types of debridement aimed at shortening the phases of the wound process with the following closure of the wound defects by different methods [1,2,5,7]. The assessment of the effectiveness of local treatment was carried out taking into account the nature and severity of the phases of the wound process by the method of clinical observation of the state of the wound (the severity of symptoms of inflammation, the nature and amount of exudate, the presence and appearance of granulations, the presence of signs of wound epithelialization and scarring, the size of the wound), microbiological, cytological and histology and research [10]. The study revealed factors that disrupt wound healing during primary surgical treatment, in the management of foci of surgical infection, in the management of postoperative wounds, in the treatment of pressure ulcers in children with neurological pathology. During the initial surgical treatment of the received wounds, its inadequacy was noted - the abandonment of necrotic, defective tissues, foreign bodies, the presence of an undiagnosed infection, the absence or inadequate antibiotic therapy, constant tension of the skin edges, impaired blood flow and innervation, inadequate sanitation and drainage. The use of modern innovative technologies in wound management reduces hospital stay, reduces the duration of the use of antibiotics and other medications, contributes to a good cosmetic effect. Application of the current innovative technologies in wounds treatment shortens the hospital stay, decreases the duration of the use of antibiotics and other medicines, and contributes to better cosmetics effects [1,4,6]. The current trends in wounds treating with the choice of local treatment according to the phases of the wound process are presented in this article. The methods of active wound defects therapy and different types of debridement considering their pros and cons are analyzed.

Bone involvement in Gaucher disease type 1: a differential diagnosis of multiple fractures in a young patient. Case report

Gaucher disease type 1 (GD1) is a rare inherited disease caused by mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase, leading to decreased enzyme activity and the consequential accumulation of its substrate, glucosylceramide, within macrophages. Bone involvement in GD1 may include avascular necrosis, bone infarcts, fragility fractures, lytic or sclerotic bone lesions and osteomyelitis. Bone pain can manifest as an acute and very painful bone crisis or a chronic pain that might vary in intensity, usually caused by fractures or avascular necrosis with progressive collapse of bone and joints. Hence, this report aims to describe a case of Gaucher disease type 1 and discuss its diagnosis, bone involvement and management, since late diagnosis or inadequate therapy can lead to clinical worsening, irreversible mobility impairment and increased morbidity. AGR, a 32-year-old male patient, was admitted to the Rheumatology Service with a previous history of diffuse bone pain, episodic hyperemia in the lower limbs since the age of 9 and two low-impact fractures. He had an initial non-confirmed diagnostic hypothesis of chronic recurrent multifocal osteomyelitis and was taking dipyrone and tramadol to reduce pain. His physical examination evinced overweight (body mass index: 29.7 kg/m2) and hepatosplenomegaly. Laboratory tests shown thrombocytopenia, with platelet count 103,000/mm3 (reference value [RV]: 140,000-450,000/mm3), serum phosphorus 4.7 mg/dL (RV: 2.7-4.5 mg/dL), C-reactive protein 88.8 mg/dL (RV: &lt; 5 mg/dL) and ferritin 1336 ng/mL (RV: 30-400 ng/mL). Biochemical and bone turnover markers were normal, including serum total calcium and magnesium, parathyroid hormone, 25-OH vitamin D, alkaline phosphatase, procollagen type-I N-terminal propeptide and C-terminal telopeptide of type I collagen. Conventional radiographies and magnetic resonance imaging were performed and confirmed previous fractures in the right humerus and the right acetabulum. They also showed sclerotic lesions in the left femur and Erlenmeyer flask deformities in the distal femurs and the proximal tibias. Bone scintigraphy indicated a bone infarct area in the left tibia. Areal bone mineral density (BMD) evaluated by bone densitometry showed a left total femur Z-score of +4.3 and left femoral neck Z-score of +4.5. Differently, the bone microarchitecture and volumetric BMD, evaluated by a high-resolution peripheral quantitative computed tomography (HR-pQCT) at distal radius and distal tibia, demonstrated an impairment of cortical compartment with lower cortical thickness and lower cortical volumetric BMD, possibly contributing to the low-impact fractures. Considering the compatible radiological findings, associated with hepatosplenomegaly and thrombocytopenia, Gaucher disease type 1 became the major hypothesis. It was confirmed after enzymatic dosage, which showed low residual glucocerebrosidase activity and high serum chitotriosidase. Enzyme replacement therapy was started with taliglucerase alfa, a recombinant enzyme preparation that aims to supply the lacking glucocerebrosidase in lysosomes. After 6 months of treatment, patient reported a significant improvement in bone pain and general quality of life. Therefore, clinicians should be alert to young patients with multiple low-impact fractures and further evaluate other possible bone involvement, as GD1 may be a differential diagnosis. Since it needs specific treatment, early diagnosis can be crucial to avoid permanent bone damage and morbidity.

Impacts of Multidrug-Resistant Pathogens and Inappropriate Initial Antibiotic Therapy on the Outcomes of Neonates with Ventilator-Associated Pneumonia.

: BackgroundIt is unknown whether neonatal ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) pathogens and inappropriate initial antibiotic treatment is associated with poor outcomes after adjusting for confounders. Methods: We prospectively observed all neonates with a definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and March 2020. All clinical features, therapeutic interventions, and outcomes were compared between the MDR–VAP and non-MDR–VAP groups. Multivariate regression analyses were used to investigate independent risk factors for treatment failure. Results: Of 720 neonates who were intubated for more than 2 days, 184 had a total of 245 VAP episodes. The incidence rate of neonatal VAP was 10.1 episodes/per 1000 ventilator days. Ninety-six cases (39.2%) were caused by MDR pathogens. Neonates with MDR–VAP were more likely to receive inadequate initial antibiotic therapy (51.0% versus 4.7%; p < 0.001) and had delayed resolution of clinical symptoms (38.5% versus 25.5%; p = 0.034), although final treatment outcomes were comparable with the non-MDR–VAP group. Inappropriate initial antibiotic treatment was not significantly associated with worse outcomes. The VAP-attributable mortality rate and overall mortality rate of this cohort were 3.7% and 12.0%, respectively. Independent risk factors for treatment failure included presence of concurrent bacteremia (OR 4.83; 95% CI 2.03–11.51; p < 0.001), septic shock (OR 3.06; 95% CI 1.07–8.72; p = 0.037), neonates on high-frequency oscillatory ventilator (OR 4.10; 95% CI 1.70–9.88; p = 0.002), and underlying neurological sequelae (OR 3.35; 95% CI 1.47–7.67; p = 0.004). Conclusions: MDR–VAP accounted for 39.2% of all neonatal VAP in the neonatal intensive care unit (NICU), but neither inappropriate initial antibiotics nor MDR pathogens were associated with treatment failure. Neonatal VAP with concurrent bacteremia, septic shock, and underlying neurological sequelae were independently associated with final worse outcomes.