Plasmodium vivax exhibits dormant liver-stage parasites, called hypnozoites, which can cause relapse of malaria. The only drug currently used for eliminating hypnozoites is primaquine. The antimalarial properties of primaquine are dependent on the production of oxidized metabolites by the cytochrome P450 isoenzyme 2D6 (CYP2D6). Reduced primaquine metabolism may be related to P. vivax relapses. We describe a case of 4 episodes of recurrence of vivax malaria in a patient with decreased CYP2D6 function. The patient was 52-year-old male with body weight of 52 kg. He received total gastrectomy and splenectomy 7 months before the first episode and was under chemotherapy for the gastric cancer. The first episode occurred in March 2019 and each episode had intervals of 34, 41, and 97 days, respectively. At the first and second episodes, primaquine was administered as 15 mg for 14 days. The primaquine dose was increased with 30 mg for 14 days at the third and fourth episodes. Seven gene sequences of P. vivax were analyzed and revealed totally identical for all the 4 samples. The CYP2D6 genotype was analyzed and intermediate metabolizer phenotype with decreased function was identified.

BACKGROUND: Transforming growth factor β (TGF-β), retinoic acid (RA), p38 mitogen-activated protein kinase (MAPK), and MEK signaling play critical roles in cell differentiation, proliferation, and apoptosis. We investigated the effect of RA and the role of these signaling molecules on the phosphorylation of Smad2/3 (p-Smad2/3) induced by TGF-β1. METHODS: A549 epithelial cells and CCD-11Lu fibroblasts were incubated and stimulated with or without all-trans RA (ATRA) and TGF-β1 and with MAPK or MEK inhibitors. The levels of p-Smad2/3 were analyzed by western blotting. For animal models, we studied three experimental mouse groups: control, bleomycin, and bleomycin+ATRA group. Changes in histopathology, lung injury score, and levels of TGF-β1 and Smad3 were evaluated at 1 and 3 weeks. RESULTS: When A549 cells were pre-stimulated with TGF-β1 prior to RA treatment, RA completely inhibited the p-Smad2/3. However, when A549 cells were pre-treated with RA prior to TGF-β1 stimulation, RA did not completely suppress the p-Smad2/3. When A549 cells were pre-treated with MAPK inhibitor, TGF-β1 failed to phosphorylate Smad2/3. In fibroblasts, p38 MAPK inhibitor suppressed TGF-β1-induced p-Smad2. In a bleomycin-induced lung injury mouse model, RA decreased the expression of TGF-β1 and Smad3 at 1 and 3 weeks. CONCLUSION: RA had inhibitory effects on the phosphorylation of Smad induced by TGF-β1 in vitro, and RA also decreased the expression of TGF-β1 at 1 and 3 weeks in vivo. Furthermore, pre-treatment with a MAPK inhibitor showed a preventative effect on TGF-β1/Smad phosphorylation in epithelial cells. As a result, a combination of RA and MAPK inhibitors may suppress the TGF-β1-induced lung injury and fibrosis.
Animals ; Apoptosis ; Bleomycin ; Blotting, Western ; Cell Differentiation ; Epithelial Cells ; Fibroblasts ; Fibrosis ; In Vitro Techniques ; Lung Injury ; Mice ; Mitogen-Activated Protein Kinase Kinases ; Mitogen-Activated Protein Kinases ; Models, Animal ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation* ; Protein Kinases ; Smad Proteins ; Transforming Growth Factor beta ; Transforming Growth Factors* ; Tretinoin*

INTRODUCTIONThis study aimed to investigate differences in the complication rate and postoperative pain score between single and multilevel surgery performed on patients with obstructive sleep apnoea.

MATERIALS AND METHODSA retrospective analysis was performed on patients with obstructive sleep apnoea who underwent surgery in a tertiary referral centre over 3 years. Patients who underwent single-level nasal, palatal or tongue surgery were compared with patients who underwent concurrent multilevel surgery of 2 or 3 levels. Complications and the postoperative Visual Analogue Scale pain score were recorded and the outcomes between single and multilevel groups were compared.

RESULTSThe overall complication rate for patients was 12.6%, 6.7% if only patients requiring intervention were considered. The adjusted odds ratio (OR) for complication rate for patients undergoing multilevel surgery and single-level surgery was 2.76. It was statistically significant (=0.053) after adjusting for confounders. There was more pain in patients who underwent multilevel surgery than in the single-level surgery group.

CONCLUSIONConcurrent multilevel surgery is a feasible option in patients with multilevel obstruction, especially if they are undergoing palate and tongue surgery, nose and palate surgery or nose and tongue surgery. There may be more complications, though it is not statistically significant. Further studies are required to investigate the differences between single-level nasal surgery and 3-level multilevel surgery. More patients undergoing multilevel surgery than single-level surgery experienced pain. Multilevel surgery patients should have their analgesia reviewed regularly and titrated accordingly.

PURPOSE: Post-operative pulmonary function is an important prognostic factor for lung transplantation. The purpose of this study was to identify factors affecting recovery of forced expiratory volume in 1 second (FEV1) at the first year after lung transplantation. MATERIALS AND METHODS: We retrospectively reviewed the medical records of lung transplantation patients between October 2012 and June 2016. Patients who survived for longer than one year and who underwent pulmonary function test at the first year of lung transplantation were enrolled. Patients were divided into two groups according to whether they recovered to a normal range of FEV1 (FEV1 ≥80% of predicted value vs. < 80%). We compared the two groups and analyzed factors associated with lung function recovery. RESULTS: Fifty-eight patients were enrolled in this study: 28 patients (48%) recovered to a FEV1 ≥80% of the predicted value, whereas 30 patients (52%) did not. Younger recipients [odds ratio (OR), 0.92; 95% confidence interval (CI), 0.87–0.98; p=0.010], longer duration of mechanical ventilator use after surgery (OR, 1.14; 95% CI, 1.03–1.26; p=0.015), and high-grade primary graft dysfunction (OR, 8.08; 95% CI, 1.67–39.18; p=0.009) were identified as independent risk factors associated with a lack of full recovery of lung function at 1 year after lung transplantation. CONCLUSION: Immediate postoperative status may be associated with recovery of lung function after lung transplantation.
Forced Expiratory Volume ; Humans ; Lung Transplantation* ; Lung* ; Medical Records ; Primary Graft Dysfunction ; Recovery of Function* ; Reference Values ; Respiratory Function Tests ; Retrospective Studies ; Risk Factors ; Ventilators, Mechanical

PURPOSE: Acute kidney injury (AKI) is common in critically ill patients. Serum cystatin C has emerged as a reliable marker of AKI. We sought to assess the value of serum cystatin C for early detection and prediction of renal function recovery in patients with sepsis. MATERIALS AND METHODS: Sepsis patients (113 AKI patients and 49 non-AKI patients) admitted to the intensive care unit (ICU) were included. Serum creatinine and cystatin C levels and glomerular filtration rate were measured on days 0, 1, 3, and 7. RESULTS: Serum cystatin C levels were significantly higher in AKI patients than in non-AKI patients at all time points. Multivariate analysis showed that only serum cystatin C levels on day 0 were associated with AKI development [odds ratio (OR)=19.30; 95% confidence interval (CI)= 2.58–144.50, p<0.001]. Linear mixed model analysis showed significant variation in cystatin C levels between the recovery and non-recovery groups over time (p=0.001). High levels of serum cystatin C at day 0 (OR=1.64; 95% CI=1.00–2.68, p=0.048) were associated with recovery of AKI. CONCLUSION: Serum cystatin C level was found to be associated with the development and worsening of AKI in ICU patients with sepsis.
Acute Kidney Injury ; Creatinine ; Critical Illness ; Cystatin C* ; Diagnosis* ; Glomerular Filtration Rate ; Humans ; Intensive Care Units ; Kidney* ; Multivariate Analysis ; Recovery of Function* ; Sepsis

Severe hyperammonemia can occur as a result of inherited or acquired liver enzyme defects in the urea cycle, among which ornithine transcarbamylase deficiency (OTCD) is the most common form. We report a very rare case of a 45-year-old Korean male who was admitted to the intensive care unit (ICU) due to severe septic shock with acute respiratory failure caused by Pneumocystis jiroveci pneumonia. During his ICU stay with ventilator care, the patient suffered from marked hyperammonemia (>1,700 µg/dL) with abrupt mental change leading to life-threatening cerebral edema. Despite every effort including continuous renal replacement therapy and use of a molecular adsorbent recirculating system (extracorporeal liver support-albumin dialysis) to lower his serum ammonia level, the patient was not recovered. The lethal hyperammonemia in the patient was later proven to be a manifestation of acquired liver enzyme defect known as OTCD, which is triggered by serious catabolic conditions, such as severe septic shock with acute respiratory failure.
Ammonia ; Brain Edema ; Humans ; Hyperammonemia* ; Intensive Care Units ; Liver ; Male ; Middle Aged ; Ornithine Carbamoyltransferase Deficiency Disease* ; Ornithine Carbamoyltransferase* ; Ornithine* ; Pneumocystis jirovecii ; Pneumonia ; Renal Replacement Therapy ; Respiratory Insufficiency ; Shock, Septic* ; Urea ; Ventilators, Mechanical

BACKGROUND: Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1) has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. METHODS: We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock) admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). RESULTS: Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively). Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029). Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038). IGF-1 level did not show significant difference between survivors and non-survivors. CONCLUSIONS: Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.
Anabolic Agents ; Cause of Death ; Critical Illness ; Humans ; Hydrocortisone ; Insulin ; Insulin-Like Growth Factor I ; Intensive Care Units ; Korea ; Liver Diseases ; Molecular Structure ; Pathologic Processes ; Physiology ; Prospective Studies ; Renin ; Sepsis* ; Shock, Septic* ; Survivors

Severe hyperammonemia can occur as a result of inherited or acquired liver enzyme defects in the urea cycle, among which ornithine transcarbamylase deficiency (OTCD) is the most common form. We report a very rare case of a 45-year-old Korean male who was admitted to the intensive care unit (ICU) due to severe septic shock with acute respiratory failure caused by Pneumocystis jiroveci pneumonia. During his ICU stay with ventilator care, the patient suffered from marked hyperammonemia (>1,700 µg/dL) with abrupt mental change leading to life-threatening cerebral edema. Despite every effort including continuous renal replacement therapy and use of a molecular adsorbent recirculating system (extracorporeal liver support-albumin dialysis) to lower his serum ammonia level, the patient was not recovered. The lethal hyperammonemia in the patient was later proven to be a manifestation of acquired liver enzyme defect known as OTCD, which is triggered by serious catabolic conditions, such as severe septic shock with acute respiratory failure.
Ammonia ; Brain Edema ; Humans ; Hyperammonemia ; Intensive Care Units ; Liver ; Male ; Middle Aged ; Ornithine Carbamoyltransferase Deficiency Disease ; Ornithine Carbamoyltransferase ; Ornithine ; Pneumocystis jirovecii ; Pneumonia ; Renal Replacement Therapy ; Respiratory Insufficiency ; Shock, Septic ; Urea ; Ventilators, Mechanical

BACKGROUND: Despite many ongoing, prospective studies on the topic, sepsis still remains one of the main causes of death in hospital. The hormone insulin-like growth factor 1 (IGF-1) has a similar molecular structure to that of insulin. IGF-1 exerts anabolic effects and plays important roles in both normal physiology and pathologic processes. Previous studies have observed low serum IGF-1 level in patients with critical illnesses. Here, we evaluated changes in IGF-1 level based on survival of septic patients. METHODS: We evaluated 140 patients with sepsis and septic shock (21 with sepsis and 119 with septic shock) admitted to the intensive care unit of a university-affiliated hospital in Korea. Serum IGF-1 level was measured on days 0, 1, 3, and 7. Patients with liver disease were excluded from this study. All data were analyzed using SPSS version 20 (SPSS Inc., Chicago, IL, USA). RESULTS: Patients with septic shock had significantly lower serum IGF-1 level on days 1 and 3 than patients without septic shock (p = 0.002 and p = 0.007, respectively). Generally, there was a negative relationship between IGF-1 and serum cortisol levels; however, this relationship was only significant on day 3 (p = 0.029). Furthermore, renin showed significantly negative correlation with IGF-1 on day 3 (p = 0.038). IGF-1 level did not show significant difference between survivors and non-survivors. CONCLUSIONS: Our results showed that IGF-1 was associated with septic shock, and that the IGF-1 axis is severely disrupted in septic patients. Additionally, serum cortisol and renin levels were associated with IGF-1 level.
Anabolic Agents ; Cause of Death ; Critical Illness ; Humans ; Hydrocortisone ; Insulin ; Insulin-Like Growth Factor I ; Intensive Care Units ; Korea ; Liver Diseases ; Molecular Structure ; Pathologic Processes ; Physiology ; Prospective Studies ; Renin ; Sepsis ; Shock, Septic ; Survivors

Hyperthyroidism is diagnosed when a patient is presented with typical symptoms, such as weight loss, palpitation, and hand tremor. However, early diagnosis is difficult in elders, because they have no typical symptoms, but only cardiovascular or muscular symptoms. In hyperthyroidism, there are often with neurologic changes, leading to various neurologic symptoms. Generalized or focal seizures are rarely reported in thyrotoxicosis and thyrotoxic crisis. Further, cases of hyperthyroidism presented as generalized seizure attack are extremely rare. We report a case of hyperthyroidism. A patient is presented at the hospital with mental change, as well as generalized seizure, who was finally diagnosed to have Graves' disease. A 56-year-old male was admitted to the hospital because of mental change with generalized seizure attack. Initial neurologic evaluations, including a brain magnetic resonance imaging and electroencephalogram proved to be normal. But, thyroid function test showed abnormal results. We diagnosed him as Graves' disease and prescribed anti-thyroid drug. Thereafter, there has been no recurrence of neurologic symptoms for 12 months.
Brain ; Early Diagnosis ; Electroencephalography ; Graves Disease ; Hand ; Humans ; Hyperthyroidism ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neurologic Manifestations ; Recurrence ; Seizures ; Thyroid Crisis ; Thyroid Function Tests ; Thyrotoxicosis ; Tremor ; Weight Loss