[Lomentospora prolificans Fungemia in a Patient With T-Cell Large Granular Leukemia: A Rare Pathogen in Türkiye]. / T-hücreli Büyük Granüler Lösemili Bir Hastada Lomentospora prolificans Fungemisi: Türkiye'de Nadir Bir Etken.

Scedosporium/Lomentospora is an opportunistic fungal pathogen found worldwide. While Scedosporium apiospermum and Scedosporium boydii are commonly observed globally, Lomentospora prolificans, which mainly affects immunosuppressed individuals, is rarely encountered and is more prevalent in arid climates, particularly in Australia and Spain. L.prolificans is a fungus commonly found in environmental sources such as contaminated water and soil. This species is known as an opportunistic pathogen that can cause deep-seated fungal infections, especially in immunosuppressed individuals. In this case report, a fatal case of L.prolificans fungemia in a patient with T-cell large granular leukemia during profound neutropenia was presented. The patient admitted to the hospital with prolonged fever, neutropenia, and shortness of breath. Antibiotherapy was administered to the patient for febrile neutropenia, but the fever persisted and his clinical status rapidly deteriorated. L.prolificans was isolated from the blood culture, and considering its antifungal resistance, combination therapy of voriconazole and terbinafine was initiated. However, the patient died of septic shock and multiple organ failure. In conclusion, although L.prolificans infections are rare, they can be life-threatening, especially in immunosuppressed individuals. Diagnosis and treatment of such infections may be difficult, therefore rapid diagnostic methods and appropriate treatment protocols should be developed. Consideration of infections caused by rare fungal pathogens in patients with risk factors may be critical for patient care. The literature review revealed that the first case of L.prolificans fungemia from Türkiye was reported in 2023. This case presentation represents the second reported case. However, in our case, L.prolificans fungemia occurred in 2018, it can be considered that L.prolificans may have been an invasive fungal pathogen of significant concern in Türkiye much earlier than previously documented.

Assessment of Admission COVID-19 Associated Hyperinflammation Syndrome Score in Critically-Ill COVID-19 Patients.

PURPOSE: We aimed to evaluate the relation between admission COVID-19 associated hyperinflammatory syndrome (cHIS) score and intensive care unit (ICU) outcomes. MATERIALS AND METHODS: Patients with laboratory confirmed COVID-19 admitted to our ICU between 20th March 2020-15th June 2021 were included. Patients who received immunomodulatory treatment except corticosteroids were excluded. Main outcomes were ICU mortality and invasive mechanical ventilation (IMV) requirement after ICU admission. RESULTS: Three hundred and seventy patients with a median (IQR) age of 66 (56-77) were analyzed. Median admission cHIS score was 3 (2-4). A cHIS score ≥3 was found to be associated with ICU mortality (sensitivity = 0.63, specificity = 0.50; p < 0.01) and IMV requirement after ICU admission (sensitivity = 0.61, specificity = 0.51; p < 0.01). Patients with an admission cHIS score ≥3 (n = 199) had worse median admission APACHEII, SOFA scores and PaO2/FiO2 ratio than others (n = 171) (p < 0.01). IMV requirement after ICU admission (38.5% vs 26.1%;p = 0.03), ICU (36.2% vs 25.1%;p = 0.02), hospital (39.1% vs 26.9%;p = 0.01) and 28th day (28.1% vs 19.1%;p = 0.04) mortality were higher in patients with admission cHIS score ≥3 than others (p < 0.01). Age <65 years, malignancy and higher admission SOFA score were independent variables associated with admission cHIS score ≥3. CONCLUSION: Critically-ill COVID-19 patients with admission cHIS score ≥3 have worse disease severity and outcomes than other patients.

The impact of COVID-19 pandemic on nosocomial multidrug-resistant bacterial bloodstream infections and antibiotic consumption in a tertiary care hospital.

We investigated the change in the epidemiology of nosocomial bloodstream infections (BSIs) caused by multidrug-resistant bacteria during Coronavirus Disease (COVID-19) and antibiotic consumption rates at a pandemic hospital and at the Oncology Hospital which operated as COVID-19-free on the same university campus. Significant increases in the infection density rate (IDRs) of BSIs caused by carbapenem-resistant Acinetobacter baumannii (CRAB) and ampicillin-resistant Enterococcus faecium (ARE) were detected at the pandemic hospital, whereas carbapenem-resistant Klebsiella pneumoniae BSIs were increased at the non-pandemic Oncology Hospital. Pulsed field gel electrophoresis showed a polyclonal outbreak of CRAB in COVID-19 intensive care units. Antibiotic consumption rates were increased for almost all antibiotics, and was most significant for meropenem at both of the hospitals. Increased IDRs of CRAB and ARE BSIs as well as an increased consumption rate of broad-spectrum antibiotics emphasize the importance of a multimodal infection prevention strategy combined with an active antibiotic stewardship program.

Comparison of critically ill COVID-19 and influenza patients with acute respiratory failure.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is one of the biggest pandemic causing acute respiratory failure (ARF) in the last century. Seasonal influenza carries high mortality, as well. The aim of this study was to compare features and outcomes of critically-ill COVID-19 and influenza patients with ARF. METHODS: Patients with COVID-19 and influenza admitted to intensive care unit with ARF were retrospectively analyzed. RESULTS: Fifty-four COVID-19 and 55 influenza patients with ARF were studied. Patients with COVID-19 had 32% of hospital mortality, while those with influenza had 47% (P=0.09). Patients with influenza had higher Eastern Cooperative Oncology Group, Clinical Frailty Scale, Acute Physiology and Chronic Health Evaluation II and admission Sequential Organ Failure Assessment (SOFA) scores than COVID-19 patients (P<0.01). Secondary bacterial infection, admission acute kidney injury, procalcitonin level above 0.2 ng/ml were the independent factors distinguishing influenza from COVID-19 while prone positioning differentiated COVID-19 from influenza. Invasive mechanical ventilation (odds ratio [OR], 42.16; 95% confidence interval [CI], 9.45-187.97), admission SOFA score more than 4 (OR, 5.92; 95% CI, 1.85-18.92), malignancy (OR, 4.95; 95% CI, 1.13-21.60), and age more than 65 years (OR, 3.31; 95% CI, 0.99-11.03) were found to be independent risk factors for hospital mortality. CONCLUSIONS: There were few differences in clinical features of critically-ill COVID-19 and influenza patients. Influenza cases had worse performance status and disease severity. There was no significant difference in hospital mortality rates between COVID-19 and influenza patients.

Do antimicrobial stewardship programs improve the quality of care in ICU patients diagnosed with infectious diseases following consultation? Experience in a tertiary care hospital.

BACKGROUND: One of the most important public health concerns is the ever-growing problem of antibiotic resistance. Importantly, the rate of introduction of new molecules into clinical practice has slowed down considerably. Moreover, the rapid emergence of resistance shortens the effective 'lifespan' of these molecules. OBJECTIVE: The quality of care before and after active intervention and feedback was evaluated in patients diagnosed with sepsis/septic shock or ventilator-associated pneumonia (VAP) in the ICUs of Hacettepe University Adult and Oncology Hospitals. RESULTS: There was a significant increase in total scores. Significant improvements were achieved in the management of these patients in terms of requests for necessary diagnostic tests, and the prolonged infusion of beta-lactam agents. CONCLUSION: Implementation of an ASP in centers where antimicrobial management of ICU patients is largely controlled by infectious diseases specialists remains a feasible strategy that leads to better patient care.

Evaluation of the blue code system established in the health campus of a university hospital.

OBJECTIVE: We report the hospital outcomes after implementing the blue code system in our hospital and health campus. We also aimed to determine factors related to mortality. METHODS: This is a retrospective observational study of the patients who received cardiopulmonary resuscitation (CPR). All blue code calls for all age groups between March 15, 2013, and April 30, 2015 were analyzed. Logistic regression analysis was performed to find independent predictors of in-hospital mortality. RESULTS: A total of 155 patients from the blue code calls were evaluated. Return of spontaneous circulation was achieved in 45.5% of patients, and 54.8% of the patients had died at the end of the CPR. The hospital discharge rate was 20%. Of all patients, 65% were adults with a survival rate of 7.9%, whereas pediatric patients had a 44.2% survival rate. Asystole and pulseless electrical activity were the predominant electrocardiography rhythms in 92.4% of patients. The comparison of survivors and nonsurvivors revealed that nonsurvivors were older, had more cancer as the comorbidity, had a more cardiac arrest, and sepsis as the underlying cause and had >20 min of CPR. The logistic regression analysis demonstrated the independent risk factors for mortality as arrest at a hospital ward, and sepsis as the underlying cause and being adult patient. CONCLUSION: The performance of the blue code system should be evaluated periodically. Every effort should be made to prevent unexpected cardiac arrests and increase hospital discharge with good neurologic outcomes.

Outcome of Patients Admitted to Intensive Care Units due to Influenza-Related Severe Acute Respiratory Illness in 2017-2018 Flu Season: A Multicenter Study from Turkey.

BACKGROUND: Influenza can cause severe acute respiratory illness (SARI), which occurs as local outbreaks or seasonal epidemics with high intensive care unit (ICU) admission and mortality rates. Mortality is mainly due to SARI. OBJECTIVE: The aim of this study was to evaluate the outcome of patients admitted to ICU due to influenza-related SARI in 2017-2018 flu season in Turkey. METHODS: A retrospective multicenter study was conducted in 13 ICUs with a total of 216 beds from 6 cities in Turkey. All adult patients (over 18 years) admitted to the ICUs in 2017-2018 flu season (between September 1, 2017, and April 30, 2018) because of SARI and with a positive nasopharyngeal swab for influenza were included in the study. RESULTS: A total of 123 cases were included in the study. The mean age of patients was 64.5 ± 17.5 years, and 66 (53.7%) patients were older than 65 years. The ICU mortality was 33.9%, and hospital mortality was 35.6%. Invasive mechanical ventilation (IMV), acute kidney injury (AKI), hematologic malignancy, and >65 years of age were the factors affecting mortality in influenza. CONCLUSION: SARI due to influenza carries a high mortality rate, and IMV, AKI, presence of hematologic malignancy, and older age are independent risk factors for mortality.

Maternal Mortality: 10 Year Experience of a Tertiary Center in Turkey.

We retrospectively evaluated five maternal mortality cases that occurred in our institution within the last 10 years. Rate of maternal mortality was 24.5 per 100000 live births. Maternal mortality causes were cardiopulmonary failure secondary to veno-occlusive disease, septic shock secondary to osteosarcoma, pulmonary thromboembolism secondary to metastatic breast cancer, septic shock secondary to cholecystitis, and postpartum hemorrhage secondary to Niemann-Pick disease. Four out of five cases were evaluated as indirect maternal mortality cases. Three out of five cases ended up with a healthy newborn, while other cases ended up with abortus and postpartum exitus.

Value of prognostic scores in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis patients in intensive care unit: a multicenter retrospective cohort study from Turkey

Background/aim: There is a need for a scoring system for predicting ICU prognosis of patients with ANCA-associated vasculitis (AAV), but there are limited data on it in the literature. Therefore, we aimed to determine the scores that can estimate the prognosis of patients with AAV during intensive care follow up. Materials and methods: All adult patients admitted to the medical ICUs of 4 reference university hospitals in Turkey due to AAV activation and/or disease/treatment complications in the last 10 years were included in this study. Demographic data, treatments before ICU, the Birmingham Vasculitis Activity Score (BVAS) score at the time of vasculitis diagnosis, and BVAS, APACHE II, SOFA, and SAPS II scores at the ICU admission, treatments, procedures, and complications during ICU stay were recorded for all AAV patients. Results: Thirty-four patients were included in the study. The median age of the patients was 60 (42­70) years, and 64.7% were male. Twenty-five patients were diagnosed with Granulomatosis with polyangiitis, and 9 were diagnosed with Microscopic polyangiitis. The most common ICU admission causes were hemorrhage (85.3%) and sepsis/septic shock (67.6%). Twenty patients (58.8%) died in the ICU follow up. There were significant differences in APACHE II (P = 0.004) and SAPS II (P = 0.044) scores between survivors and nonsurvivors, while there were no significant differences in BVAS (during diagnosis P = 0.089 and ICU admission P = 0.539) and SOFA (P = 0.097) scores. APACHE II score was found to be an independent risk factor for ICU mortality (OR = 1.231, CI 95% = 1.011­1.498, P = 0.038) according to logistic regression analysis. An APACHE II score of greater than 20.5 predicted ICU mortality with 80% sensitivity and 70% specificity (AUC = 0.8, P = 0.004, Likelihood ratio = 2.6) according to the ROC curve analysis. Conclusion: APACHE II score can be used for the prediction of ICU mortality in AAV patients.

The effect of the first-year residents orientation period on intensive care and hospital mortality, in a medical intensive care unit, within a developing country.

PURPOSE: To determine whether the adaptation of junior residents, during their first week rotation period within the ICU, has any effect on ICU and hospital mortality rates, in a developing country. MATERIALS AND METHODS: Patients who were admitted to the ICU were included, with 1207 out of 1547 of the admitted patients being eligible. The effect of age, gender, co-morbidities, the cause of the ICU admission, the presence of hospital-acquired infections, residents rotation week, admission time (weekday vs. weekend), number of patients admitted on the same day (one vs. two or more) and APACHE II score upon the ICU and hospital mortality rates were evaluated. RESULTS: The first rotation week of junior residents is an independent risk factor determining hospital mortality (OR (95% CI) = 2.42 (1.23-4.76); p = .010). The effect of the first rotation week on intensive care mortality was not statistically significant (1.92 (0.97-3.84); p = .063). In addition, the presence of malignancy, sepsis-septic shock, hospital-acquired infection and high APACHE II score were found to be other independent determinants of increased hospital mortality. CONCLUSION: The junior residents first rotation week is an independent risk factor on hospital mortality, in a tertiary medical intensive care unit, within a developing country.

Acute eosinophilic pneumonia secondary to heroin inhalation.

Smoking heroin (chasing the dragon), is a method of inhaling heroin via heating the drug on a tin-foil above a flame. It also has been associated both with the indirect effects of heroin overdose and with direct pulmonary toxicity. We describe a case of acute eosinophilic pneumonia secondary to heroin inhalation in our medical intensive care unit. She presented with fever, cough, dyspnea and pleuritic chest pain. Chest radiograph showed bilateral infiltrations. Examination of bronchoalveolar lavage fluid revealed significant eosinophilia. She was diagnosed with acute eosinophilic pneumonia. After heroin abstinence and corticosteroid therapy, remission was achieved rapidly and the patient was discharge on the fourth day of her hospital stay.

Factors associated with pulmonary hypertension and long-term survival in bronchiectasis subjects.

BACKGROUND: The development of pulmonary hypertension (PH) and its effect on long-term survival in bronchiectasis subjects has not been explored. The present study aims to analyze the factors associated with PH and its effect on long-term survival in bronchiectasis subjects. METHODS: We prospectively evaluated 23 bronchiectasis subjects without PH and 16 with PH, as well as 20 healthy volunteers. RESULTS: Bronchiectasis subjects with PH were more hypoxemic and had a greater number of involved lobes in high resolution computed tomography (HRCT) than did the bronchiectasis subjects without PH (P < 0.001 and P < 0.001, respectively). At three years, the survival rate was 95.7% for bronchiectasis subjects without PH and 56.3% for bronchiectasis with PH, and at 5 years, these rates were 95.7% and 62.5%, respectively (P = 0.002). Multivariate Cox regression analysis revealed that only the Medical Research Council (MRC) dyspnea score was independently related to poor survival in all bronchiectasis subjects (hazard ratio: 6.98; 95% CI: 2.41-20.23; P < 0.00001). CONCLUSIONS: Subjects with PH are more hypoxemic and have a greater number of involvements in the lobes of the lungs. Bronchiectasis subjects with PH have worse survival than do bronchiectasis subjects without PH. MRC dyspnea score is an independent predictor of long-term survival.

Investigation of hemophagocytic lymphohistiocytosis in severe sepsis patients.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled inflammation and has common clinical and laboratory features with sepsis. The aim of this study was to investigate patients treated with severe sepsis who had bicytopenia for the presence of HLH. MATERIALS AND METHODS: Patients with severe sepsis who were non-responsive to treatment and developed at least bicytopenia were included. Peripheral blood samples were collected and stored for later evaluation for natural killer (NK) activity and soluble interleukin-2 receptor levels. Diagnostic criteria of HLH were retrospectively analyzed. RESULTS: Seventy-five of 382 patients (20%) were followed as severe sepsis and septic shock. Among them, 40 patients had bicytopenia. Twenty-six of 40 patients were excluded due to the presence of active solid or hematological malignancies. Three patients died before fulfillment of HLH criteria and one patient denied to give consent. All of the remaining 10 patients had at least five of the eight criteria according to criteria of the Histiocyte Society. Only one of 10 patients was diagnosed as HLH and received treatment during intensive care unit stay. None of the 10 patients survived. CONCLUSIONS: This study emphasizes to consider the possibility of HLH and the need of rapid assessment of patients with severe sepsis who had bicytopenia and were resistant to treatment in intensive care.

Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies.

BACKGROUND: Estimating attributable mortality of ventilator-associated pneumonia has been hampered by confounding factors, small sample sizes, and the difficulty of doing relevant subgroup analyses. We estimated the attributable mortality using the individual original patient data of published randomised trials of ventilator-associated pneumonia prevention. METHODS: We identified relevant studies through systematic review. We analysed individual patient data in a one-stage meta-analytical approach (in which we defined attributable mortality as the ratio between the relative risk reductions [RRR] of mortality and ventilator-associated pneumonia) and in competing risk analyses. Predefined subgroups included surgical, trauma, and medical patients, and patients with different categories of severity of illness scores. FINDINGS: Individual patient data were available for 6284 patients from 24 trials. The overall attributable mortality was 13%, with higher mortality rates in surgical patients and patients with mid-range severity scores at admission (ie, acute physiology and chronic health evaluation score [APACHE] 20-29 and simplified acute physiology score [SAPS 2] 35-58). Attributable mortality was close to zero in trauma, medical patients, and patients with low or high severity of illness scores. Competing risk analyses could be done for 5162 patients from 19 studies, and the overall daily hazard for intensive care unit (ICU) mortality after ventilator-associated pneumonia was 1·13 (95% CI 0·98-1·31). The overall daily risk of discharge after ventilator-associated pneumonia was 0·74 (0·68-0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91-2·54). Highest cumulative risks for dying from ventilator-associated pneumonia were noted for surgical patients (2·97, 95% CI 2·24-3·94) and patients with mid-range severity scores at admission (ie, cumulative risks of 2·49 [1·81-3·44] for patients with APACHE scores of 20-29 and 2·72 [1·95-3·78] for those with SAPS 2 scores of 35-58). INTERPRETATION: The overall attributable mortality of ventilator-associated pneumonia is 13%, with higher rates for surgical patients and patients with a mid-range severity score at admission. Attributable mortality is mainly caused by prolonged exposure to the risk of dying due to increased length of ICU stay. FUNDING: None.

Effect of enteral versus parenteral nutrition on outcome of medical patients requiring mechanical ventilation.

BACKGROUND: Early enteral nutrition (EN) in patients receiving mechanical ventilation commonly has been advocated, based mainly on studies conducted in mixed populations of trauma and surgery patients. In this study, ventilator-associated pneumonia rates and outcomes were compared in mechanically ventilated medical intensive care unit (ICU) patients receiving enteral versus parenteral nutrition. METHODS: Patients fulfilling inclusion criteria between February 1, 2004, and January 31, 2006, were included. Patients were randomized to enteral or parenteral nutrition (PN) within 48 hours of intubation. Development of ventilator-associated pneumonia, assessment as to whether day feeding goal was attained, duration of mechanical ventilation, ICU and hospital length of stay (LOS), and mortality rates were recorded. RESULTS: Of 249 consecutive patients receiving mechanical ventilation, 71 patients were included. Thirty (42.3%) patients received EN, and 41 (57.7%) received PN. There was no difference between groups for age, sex, body mass index, and scores on the Acute Physiology and Chronic Health Evaluation II. Ventilator-associated pneumonia rate, ICU and hospital LOS, and mortality rates were similar for both groups. In the parenterally fed group, duration of mechanical ventilation was longer (p = .023), but the feeding goal was attained earlier (p = .012). CONCLUSIONS: In mechanically ventilated patients in the medical ICU, ventilator-associated pneumonia rates, ICU and hospital lengths of stay, and ICU and hospital mortality rates of patients receiving PN are not significantly different than those in patients receiving EN, and feeding goals can more effectively be attained by PN. Yet, duration of mechanical ventilation is slightly longer in patients receiving PN.

Spectrum of practice in the diagnosis of nosocomial pneumonia in patients requiring mechanical ventilation in European intensive care units.

OBJECTIVES: Information on clinical practice regarding the diagnosis of pneumonia in European intensive care units is limited. The aim of this study was to describe the spectrum of actual diagnostic practices in a large sample of European intensive care units. DESIGN: Prospective, observational, multicenter study. SETTING: Twenty-seven intensive care units of nine European countries. PATIENTS: Consecutive patients requiring invasive mechanical ventilation for an admission diagnosis of pneumonia or receiving mechanical ventilation for >48 hrs irrespective of admission diagnosis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2,436 patients were evaluated; 827 were admitted with or developed nosocomial pneumonia (hospital-acquired pneumonia [HAP], 27.1%; ventilator-associated pneumonia [VAP], 56.2%; very early onset VAP, 16.7%). Mean age was 59.4 +/- 18.1 yrs, 65.0% were men, and mean admission Simplified Acute Physiology Score II was 46.7 +/- 17.1. Worsening oxygenation (76.8%), purulent/changing respiratory secretions (72.1%), and new temperature elevation (69.2%) were the most frequent clinical signs of nosocomial pneumonia. Etiological diagnosis was based on noninvasive respiratory specimens in 74.8% of episodes. Bronchoscopy was performed in 23.3% of episodes. Bronchoscopy performance, after adjustment by severity of illness, age, and type of hospital, were predicted by worsening oxygenation (odds ratio 2.03; 95% confidence interval, 1.27-3.24) and male sex (odds ratio 1.77; 95% confidence interval, 1.19-2.65). Definite cause was documented in 69.5% of nosocomial pneumonia cases. The most common isolates were Staphylococcus aureus (16.3% methicillin-sensitive S. aureus and 16.0% methicillin-resistant S. aureus), Pseudomonas aeruginosa (23.1%), and Acinetobacter baumannii (19.1%). Presence of nosocomial pneumonia significantly prolonged mean length of mechanical ventilation (10.3 days, p < .05) and mean intensive care unit length of stay (12.2 days, p < .05) in intensive care unit survivors. Mortality rate was 37.7% for nosocomial pneumonia vs. 31.6% for patients without pneumonia (p < .05). CONCLUSIONS: Etiological diagnosis of nosocomial pneumonia in a large sample of European intensive care units was based mainly on noninvasive techniques. However, there was high variability in bronchoscopy use between the participating intensive care units.

Rhabdomyolysis in a patient treated with colchicine and atorvastatin.

OBJECTIVE: To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. CASE SUMMARY: A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50-fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. DISCUSSION: Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. CONCLUSIONS: We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.

Concurrent presentations of the sarcoidosis, tuberculosis and lymphoma in a single patient.

A 56-year-old female patient, developing ALK-negative anaplastic T cell lymphoma 7 years after the diagnosis of sarcoidosis with clinical and histopathological features of tuberculosis has been presented. We herein present concurrent occurrence of the sarcoidosis, lymphoma and tuberculosis along with the confusing findings during the investigation for the establishing the diagnosis and management that represented a great challenge.

Effect of lung volume reduction surgery on diaphragmatic neuromechanical coupling at 2 years.

STUDY OBJECTIVES: We previously reported that patients with emphysema show an increase in diaphragmatic neuromechanical coupling at 3 months after lung volume reduction surgery. Diaphragmatic neuromechanical coupling was quantified as the quotient of tidal volume (normalized to total lung capacity) to tidal change in transdiaphragmatic pressure (normalized to maximal transdiaphragmatic pressure). As such, neuromechanical coupling estimates the fraction of diaphragmatic capacity used to generate tidal breathing. The present investigation was conducted to determine whether benefit is maintained at 2 years. SUBJECTS: Fifteen patients with severe COPD, 8 of whom completed the 2-year study. METHODS: Lung volumes, exercise capacity (6-min walking distance), diaphragmatic function (maximal transdiaphragmatic pressure and twitch transdiaphragmatic pressure elicited by phrenic nerve stimulation), and diaphragmatic neuromechanical coupling were recorded before surgery, and at 3 months and 2 years after surgery. RESULTS: Two years after surgery, lung volumes deteriorated to preoperative values, but patients showed persistent improvements in 6-min walking distance (p < 0.05). Three months after surgery, maximal transdiaphragmatic pressure (p < 0.05), twitch transdiaphragmatic pressure (p < 0.01), and diaphragmatic neuromechanical coupling (p < 0.01) had increased over preoperative values. The improvements in neuromechanical coupling resulted from improvements in diaphragmatic strength and, to a lesser extent, from a decrease in transdiaphragmatic pressure required to maintain tidal breathing. The change in respiratory muscle function at 2 years varied among patients: diaphragmatic contractility was > 10% of preoperative value in half of the patients who concluded our study, and neuromechanical coupling was > 10% of preoperative value in three fourths of the patients who concluded our study. Patients who maintained their gains in neuromechanical coupling also maintained their gains in 6-min walking distance. CONCLUSION: Patients undergoing lung volume reduction surgery can maintain early gains in neuromechanical coupling and exercise capacity 2 years later.