Sarcopenia diagnosis in patients with colorectal cancer:a review of computed tomography-based assessments and emerging ways to enhance practicality

Traditionally, cancer treatment has focused on the stages of the disease; however, recent studies have highlighted the importance of considering the overall health status of patients in the prognosis of cancer. Loss of skeletal muscle, known as sarcopenia, has been found to significantly affect outcomes in many different types of cancers, including colorectal cancer. In this review, we discuss the guidelines for diagnosing sarcopenia, with a specific focus on CT-based assessments. Many groups worldwide, including those in Europe and Asia, have introduced their own diagnostic guidelines for sarcopenia. Seemingly similar yet subtle discrepancies, particularly in the cutoff values used, limit the use of these guidelines in the general population, warranting a more universal guideline. Although CT-based measurements, such as skeletal muscle index and radiodensity, have shown promise in predicting outcomes, the lack of standardized values in these measurements hinders their universal adoption. To overcome these limitations, innovative approaches are being developed to assess changes in muscle mass trajectories and introduce new indices, such as skeletal and appendicular muscle gauges. Additionally, machine learning models have shown superior performance in predicting sarcopenic status, providing an alternative to CT-based diagnosis, particularly after surgery. CT has tremendous benefits and a significant role in visually as well as quantitatively retrieving information on patient body composition. In order to compensate for the limitation of standard cutoff value, 3-dimensional analysis of the CT, artificial intelligence-based body composition analysis, as well as machine learning algorithms for data interpretation and analysis have been proposed and are being utilized. In conclusion, despite the varying definitions of sarcopenia, CT-based measurements coupled with machine-learning models are promising for evaluating patients with cancer. Standardization efforts can improve diagnostic accuracy, reduce the reliance on CT examinations, and make sarcopenia assessments more accessible in clinical settings.

Comparing extracorporeal, semi-extracorporeal, and intracorporeal anastomosis in laparoscopic right hemicolectomy: introducing a bridging technique for colorectal surgeons

Purpose@#Intracorporeal anastomosis (IA) in laparoscopic right hemicolectomy has been associated with faster recovery in bowel function compared to extracorporeal anastomosis (EA). However, the technical difficulty of laparoscopic suturing technique and intraabdominal fecal contamination hinder many surgeons from implementing such a procedure. We introduce and compare a bridging technique designated as “semi-extracorporeal” anastomosis (SEA), which embraces the advantages and amends the drawbacks of IA and EA. @*Methods@#Between May 2016 and October 2022, 100 patients who underwent laparoscopic right hemicolectomy were analyzed. All patients who received laparoscopic right hemicolectomy underwent one of the 3 anastomosis methods (EA, SEA, and IA) by a single colorectal surgeon at a single tertiary care hospital. Data including perioperative parameters and postoperative outcomes were analyzed by each group. @*Results@#A total of 100 patients were reviewed. Thirty patients underwent EA; 50 and 20 patients underwent SEA and IA, respectively. Operation time (minute) was 170 (range, 100–285), 170 (range, 110–280), and 147.5 (range, 80–235) in EA, SEA, and IA, respectively (P = 0.010). Wound size was smaller in SEA and IA compared to EA (P < 0.001). IA was associated with a shorter time (day) to first flatus compared to SEA and EA (4 [range, 2–13] vs. 4 [range, 2–7] vs. 2.5 [range, 1–4], P < 0.001).Postoperative complication showed no statistical significance between the 3 groups. @*Conclusion@#Semi-extracorporeal was an attractive bridging option for colorectal surgeons worrisome of the technical difficulty of IA while maintaining faster bowel recovery and smaller wound incisions compared to EA.

Neonatologist-Performed Cranial Ultrasonography in the Neonatal Intensive Care Unit

Cranial ultrasound (CUS) is an initial screening imaging tool used to evaluate the neonatal brain. It is an accessible, inexpensive, and harmless technique that can be used at bedside as frequently as required. Timely focused CUS in the neonatal care unit can play a major role in the diagnosis, follow-up, and management of brain damage. Despite the increasing use of point-of-care ultrasonography by intensive care physicians, neonatologist-performed CUS remains unusual. This review aims to provide an overview of neonatal CUS to neonatologists, focusing on the optimal settings, standard planes of the brain, and main pathologies in preterm infants. Adding Doppler studies allows evaluation of the patency of intracranial arteries and veins, flow velocities, and indices. This may provide an opportunity for earlier targeted circulatory support to prevent brain injury and improve long-term neurodevelopmental outcomes.

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have been reported in anti-PD-1 antibodies such as pembrolizumab and nivolumab. We here report a case of intestinal perforation in a patient treated with nivolumab.

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have been reported in anti-PD-1 antibodies such as pembrolizumab and nivolumab. We here report a case of intestinal perforation in a patient treated with nivolumab.

Central line-associated bloodstream infections in neonates / 소아과

Newborn infants, including premature infants, are high-risk patients susceptible to various microorganisms. Catheter-related bloodstream infections are the most common type of nosocomial infections in this population. Regular education and training of medical staffs are most important as a preventive strategy for central line-associated bloodstream infections (CLABSIs). Bundle approaches and the use of checklists during the insertion and maintenance of central catheters are effective measures to reduce the incidence of CLABSIs. Chlorhexidine, commonly used as a skin disinfectant before catheter insertion and dressing replacement, is not approved for infants <2 months of age, but is usually used in many neonatal intensive care units due to the lack of alternatives. Chlorhexidine-impregnated dressing and bathing, recommended for adults, cannot be applied to newborns. Appropriate replacement intervals for dressing and administration sets are similar to those recommended for adults. Umbilical catheters should not be used longer than 5 days for the umbilical arterial catheter and 14 days for the umbilical venous catheter. It is most important to regularly educate, train and give feedback to the medical staffs about the various preventive measures required at each stage from before insertion to removal of the catheter. Continuous efforts are needed to develop effective and safe infection control strategies for neonates and young infants.

Seasonality and etiology of croup in pediatric patients hospitalized with lower respiratory tract infections: A long-term study between 2009 and 2017

PURPOSE: Croup is a common respiratory disease in children. The aim of this study was to analyze the epidemiology, etiology, and seasonal variations of respiratory virus infections in children with croup. METHODS: From October 2009 to September 2017, children admitted with croup to Gachon University Gil Medical Center under the age of 18 years were enrolled in this study. We retrospectively reviewed patients' medical records. RESULTS: A total of 1,053 of 27,330 patients (3.9%) infected with lower respiratory infections were diagnosed as having croup. In the age distribution, croup was most common (50.0%) in children aged 1 to <2 years. There were 2 peaks, the major in summer (July to August) and the minor in spring (March to May). Parainfluenza virus type 1 (15.8%) was most prevalent and coincided with the summer peaks of croup. Influenza virus type B and parainfluenza virus type 3 were the most frequent etiologic agents in a spring peak of croup. Although parainfluenza virus type 1 was predominant of all ages, human coronavirus was a significant cause of croup in children younger than 1 year, whereas influenza virus played an important role in children above the age of 3 years. CONCLUSION: Seasonality and epidemiology of croup varied with age and regions. Two peaks of seasonal fluctuation were in summer and spring, which were related to the seasonality of respiratory viruses in croup. These results may be helpful in planning clinical and research needs.

Epidemiology of Staphylococcus aureus Bacteremia in Children at a Single Center from 2002 to 2016

PURPOSE: We aimed to investigate the epidemiological characteristics of Staphylococcus aureus bacteremia in Korean children. METHODS: We retrospectively collected and analyzed data from the medical records of the patients with S. aureus bacteremia ≤18 years of age in Gil Medical Center from 2002 to 2016. RESULTS: A total of 212 SAB cases were detected. The annual incidence of SAB from 2002 to 2016 ranged from 0.77 to 1.95 per 1,000 patients hospitalized. The neonate group (<28 days of age) and the pediatric group (28–18 years of age) were 51.4% (n=109) and 48.6% (n=103), respectively. According to the origin of infection, there were 93 cases (43.9%) of community-associated (CA)-SAB and 119 cases (56.1%) of healthcare-associated (HA)-SAB. The rates of HA-SAB among the neonate group and among the pediatric group were 64.2% and 47.6%, respectively (P=0.015). There was no difference in complications between CA-SAB and HA-SAB, but mortality was higher in HA-SAB. The proportion of methicillin-resistance S. aureus (MRSA) was the highest in neonates (88.1%), decreased with age, and was 36.4%–37.5% among children aged ≥5 years. The MRSA proportion was 72.2%, showing no consistent trend over the period. CONCLUSIONS: The annual incidence of SAB and the proportion of MRSA in SAB remained constant in the recent 15 years in children. Judicious decision of antimicrobial agents for treatment considering the patient's age and the origin of infection is necessary.

Pharmacokinetics and drug therapy in neonates

Neonates include both full term and preterm infants up to 28 days of age. The heterogeneity and rapid physiologic change of neonates affect all aspects of pharmacokinetics such as absorption, distribution, metabolism, and elimination. This feature should be considered in determining the dose and regimen of drug therapy in neonates. However, the research on the safety and efficacy of specific drugs is limited due to ethical and technical issues. This review article focuses on the neonatal pharmacokinetics and the rationales of drug therapy in neonates based on findings of previous studies and empirical evidence.

Alteration of Akt, p-Akt, ERK, and p-ERK Proteins Expression in the Kidney of Hypokalemic Rat / 체질인류학회지

Hypokalemia causes metabolic alkalosis and morphological changes of the kidney. K⁺ balance is regulated not only by ion channels or pump gene, but also by various genes including NF-E2-related factor 2 (Nrf2). Previous study suggested the possibility that Akt and ERK kinase may be involved in Nrf2 transcriptional gene activation. In present study, we investigate the alterations of Akt, p-Akt, ERK, p-ERK protein in both normal kidney and K⁺-deficient diet kidney using Western blot analysis, and immunohistochemisrty. Our western blot data showed that the expression of Akt and p-Akt was increased gradually in K⁺-depleted diet (from 1W-3W) compared to normal group. The expression of ERK and p-ERK was markedly increased in K⁺-depleted diet 2W in comparison with normal group. Based on our immunostaining results, Akt protein immunoreactivity was prominently increased in outer medullary collecting duct, especially in K⁺-depleted diet 2 weeks. The localization of p-Akt proteins in K⁺-depleted groups was not different from normal group, but the immunoreactivity was significantly increased in distal convoluted tubule, macula densa and outer medullary thick ascending limb in K⁺-depleted diet 1 and 2 weeks groups. ERK protein immunoreactivity was prominently increased in outer medullary collecting duct, especially in K⁺-depleted diet 2 and 3 weeks. The localization of p-ERK proteins in K⁺-depleted groups was not different from normal group, but the immunoreactivity was prominently increased in the nucleus of outer medullary collecting duct especially in K⁺-depleted diet 2 weeks. Taken together, we suggest that the expression of p-Akt was gradually increased in K⁺-depleted groups of kidney, but the expression of p-ERK was markedly increased in K⁺-depleted diet 2 week group. Hence, the promotion of AKT and ERK phosphorylation in hypokalemic condition may be involved in the regulation of ion channels, ion transporters and subsequent intracellular signal transduction.

Comparison of etiology and clinical presentation between children with laryngotracheobronchopneumonitis and croup

PURPOSE: Croup, a common childhood respiratory illness with various severities, has many unanswered questions. Laryngotracheobronchopneumonitis (LTBP) is a disease entity considered to be an extension of croup to the lower respiratory tract. The object of this study was to compare epidemiology, clinical characteristics, and viral etiologic spectrum between croup and LTBP. METHODS: Patients hospitalized with croup at Gachon University Gil Hospital from January 2010 to April 2016 were recruited. LTBP was defined as pneumonia confirmed on radiographs of patients with croup. Clinical findings and demographic data were reviewed of patients whose nasopharyngeal swabs were done for viral analysis. RESULTS: A total of 371 patients with only croup and 63 patients with LTBP were included. Croup was found to be significantly associated with parainfluenza virus type 1 (P=0.006). LTBP was related to parainfluenza virus type 3, respiratory syncytial virus, and human bocavirus (P=0.001, P=0.030, and P=0.019, respectively). The duration of fever was longer in patients with LTBP than in those with croup (3.87±1.85 days vs. 2.86±1.80 days, P<0.001). CONCLUSION: Specific etiologic viruses might be associated with the progression from croup to LTBP. Pronged fever is also associated with progression from croup to LTBP.

Serotype Distribution of Invasive Group B Streptococcal Diseases in Infants at Two University Hospitals in Korea

PURPOSE: This study was aimed at analyzing the serotypes of group B streptococcus (GBS) isolated from Korean infants with invasive disease and evaluating their association with disease manifestation. METHODS: Data were retrospectively collected from invasive GBS infections at Gachon University Gil Medical Center from January 2006 to June 2012 and at Samsung Medical Center from April 2010 to November 2012. Serotypes were determined by slide agglutination test. RESULTS: A total of 37 cases were identified, which included 22 full-term infants and 15 preterm infants. Fifteen cases (40.5%) were early-onset, 19 (51.4%) was late-onset, and three (8.1%) was very late-onset. Early-onset diseases among preterm infants were higher than those among full-term infants (60.0% [9/15] vs. 27.3% [6/22], P =0.17). The most common manifestation was bacteremia (70.3%), followed by meningitis and septic arthritis. Among 24 isolates retrievable for serotyping, serotype III (41.7%) was most common, followed by V (16.7%), Ia, Ib, and II (12.5%, respectively), and non-typeable (4.2%). Serotype III was more common in isolates from full-term infants (10/22) than from preterm infants (0/15), whereas serotype V was more common in isolates from preterm infants (4/15) than from full-term infants (0/22) (P =0.002). No penicillin-resistant strain was detected, and resistance to erythromycin and clindamycin were both 64.9%. CONCLUSIONS: GBS is an important pathogen in both preterm and full-term infants, and serotype distribution of GBS causing invasive diseases can differ between preterm and full-term infants. It is necessary to monitor the nationwide epidemiology of GBS diseases, including in preterm infants, in order to prepare preventive measures without underestimating early-onset diseases.

Alteration of Nrf2 and p-Nrf2 Protein Expression in Hypokalemic Rat Kidney / 체질인류학회지

Potassium (K) balance is regulated not only by ion channels and ion transporters, but also by various genes including NF-E2-related factor 2 (Nrf2). Although mRNA distribution and role of Nrf2 has been studied in hypokalemic kidney, the distribution of Nrf2 and phosphorylated-Nrf2 (p-Nrf2) proteins are not known. The present study was planned to examine the alteration of expression and distribution of Nrf2 and p-Nrf2 protein in the kidney of normal and K-depleted rats using immunohistochemistry. In normal rat kidneys, Nrf2 was highly expressed in the proximal convoluted tubule and proximal straight tubule, moderately in cortical thick ascending limb, and weakly in cortical collecting duct, outer medullary thick ascending limb, and outer medullary collecting duct. In K-depleted groups, the pattern of cellular labeling of Nrf2 protein was identical to that of normal group, but the signal intensity was prominently increased in proximal convoluted tubule and proximal straight tubule especially in rats at K-free diet 3 weeks. In normal rat kidneys, p-Nrf2 was highly expressed in nucleus of cortical thick ascending limb, cortical collecting duct, and glomerular endothelial cell, moderately in distal convoluted tubule and outer medullary collecting duct, and weakly in proximal convoluted tubules and outer medullary thick ascending limb. In K-depleted groups, the pattern of cellular labeling of p-Nrf2 protein was similar to that of normal group, but signal intensity was significantly increased in the nucleus of outer medullary collecting duct from of K-free diet 2 and 3 weeks groups. These results suggest that Nrf2 and p-Nrf2 expression was gradually increased in K-depleted groups of kidney, but Nrf2 and p-Nrf2 expression patterns were not exactly matched. In addition, it is suggested that enhanced expression of Nrf2 and p-Nrf2 in hypokalemic condition may affect the regulation of ion channels and ion transporters and subsequent intracellular signal transduction.

Clinical presentations of Chlamydia pneumoniae in children hospitalized for acute respiratory infections: a comparison to Mycoplasma pneumonia

PURPOSE: Chlamydia pneumoniae is a common intracellular bacterial pathogen and plays an important role in acute respiratory infections. The purpose of this study was to investigate clinical presentations of C. pneumoniae in children with acute respiratory infections. METHODS: We examined the medical records of pediatric patients (age<18 years) admitted with acute respiratory infections of C. pneumoniae to Gachon University Gil Medical Center between March 1, 2011 and August 31, 2014. We compared the clinical features of C. pneumoniae infection with that of Mycoplasma pneumoniae infection. RESULTS: We confirmed acute respiratory infections of C. pneumoniae in 110 patients out of 2,156 patients (5.1%) admitted with acute respiratory infections. The mean age was 37.2+/-30.1 months. More than half of them (54.5%) had coinfection. C. pneumoniae infection had mild and subacute courses. The mean duration of symptoms prior to admission was 8.5+/-13.8 days. There were remarkable seasonal variations and prevalence was higher in December and April (P=0.03 and P=0.02, respectively). Although rhinorrhea and pharyngeal injection were more common in C. pneumoniae infection (P<0.05), clinical signs and symptoms were similar between C. pneumoniae and M. pneumoniae. Extrapulmonary manifestations such as skin lesion, Gastrointestinal symptoms, hepatitis, and neurologic symptoms were common (41.0%) in C. pneumoniae infection and, had similar incidence in M. pneumoniae infection. CONCLUSION: C. pneumoniae is an important infectious agent of acute respiratory infections in children. Clinical pictures of C. pneumoniae are similar to M. pneumoniae, even in extrapulmonary manifestations. C. pneumoniae should be taken into consideration in differential diagnosis of acute respiratory infection in children.

The Impact of Fluid Therapy Strategies on Nonoliguric Hyperkalemia in Extremely Low Birth Weight Infants

PURPOSE: The aim of this study was to characterize the changes in the incidence and clinical characteristics of nonoliguric hyperkalemia (NOHK), together with plasma potassium levels, according to the fluid therapy strategies for extremely low birth weight infants (ELBWIs) during the first few days of life. METHODS: This retrospective study enrolled ELBWIs. We analyzed the occurrence of NOHK, plasma potassium levels, other biochemical data, and fluid balances according to historically controlled strategies such as conventional limited-volume supply and low-dose calcium supplementation (P1), increased-volume supply and high-dose calcium supplementation (P2), and early aggressive nutrition (EAN) and high-dose calcium supplementation (P3). RESULTS: The incidence of NOHK and the plasma potassium levels in P2 (127 ELBWIs) were not different from those in P1 (39 ELBWIs). However, arrhythmia and fatality significantly decreased in P2 compared to those in P1. In P3 (68 ELBWIs), the incidence of NOHK after 24 h and the plasma potassium levels after 36 h of life were significantly reduced compared to those in P1 and P2. Neither arrhythmia nor fatality developed in P3. CONCLUSION: EAN combined with high-dose calcium supplementation could be a potential strategy for the prevention of NOHK along with consequent arrhythmia and fatality in ELBWIs.

Clinical Features of Late-onset Circulatory Collapse in Preterm Infants / 대한주산의학회잡지

PURPOSE: We aimed to describe the clinical features of late-onset circulatory collapse (LCC) in preterm infants. METHODS: The records of preterm infants with a gestational age of <33 weeks who were admitted to a single neonatal intensive care unit and survived more than 72 hrs between March 2006 and August 2012 were reviewed retrospectively. RESULTS: Of the total of 659 patients, 44 (6.7%) were diagnosed with LCC. Their mean gestational age was 26.0+/-1.9 weeks and their median birth weight 830 g. The median time of onset of LCC was 16.5 postnatal days. The patients exhibited oliguria that responded to hydrocortisone but not to hydration or catecholamines. Other clinical features of LCC were hypotension (73%), hyponatremia (52%), and hyperkalemia (34%). These abnormalities resolved in sequence: oliguria resolved first, after a median of 2.2 hrs, followed by hypotension after a median of 3.0 hrs, and the serum Na level became normal after 12.9 hrs. The incidence of LCC increased as the gestational age and/or birth weight decreased. A total of 26 patients (59%) developed LCC within 2 weeks after the initiation of levothyroxine therapy. CONCLUSION: LCC in preterm infants was a relatively reversible condition but could be associated with severe morbidity. We therefore recommend the implementation of careful measures for early detection and prompt management of LCC, particularly after stressful events.

Using the High Frequency Ventilation during Neonatal Transport

PURPOSE: To present and evaluate a system of high-frequency oscillatory ventilator (HFOV) during intra-/inter-hospital neonate transport. METHODS: The system includes a charged HFOV (SOPHIE, Fritz Stephan GmbH, Dusseldorf, Germany), an incubator, and E-oxygen/air-cylinders with connections to the HFOV. The test lung was evaluated at the high and medium ventilator settings used for infants to determine the operating time of HFOV. The time required to exhaust the gas supply was checked, and the HFOV was operated until the low-battery alarm sounded to determine the operating time of the batteries. RESULTS: The batteries provided electrical power for at least 60 mins, and the oxygen and air-cylinders lasted at least 20 mins. The system has been used frequently for the intra-hospital transport, from delivery rooms to ICU and from ICU for surgery. The system has been used twice for the inter-hospital transport of infants with bronchopulmonary dysplasia and pulmonary hypertension to another hospital 45 km away (one hour distance). In one case, the ambulance's electrical power supply failed, causing the system failure during the last 5 mins of transport. However, with the complete check and simulation of the system and the ambulance bulk oxygen/electric supply, the second patient was transported successfully in stable condition. CONCLUSION: The system was useful for intra-/inter-hospital transport of the neonates on HFOV. For the transport time of 60 mins, fully charged HFOV, 2 E-oxygen-cylinders, and 3 E-air-cylinders seemed to be sufficient. H-oxygen-cylinder and ambulance electrical power supply should also be provided for safe and efficient transport between hospitals.

Initiation of Therapeutic Hypothermia with a Cooling Fan for an Asphyxiated Newborn

Induced hypothermia for newborns with hypoxic-ischemic encephalopathy results in a significant decrease in mortality and neurodevelopmental disability. For optimal neuroprotection following perinatal hypoxia-ischemia (HI), therapy should begin within 6 hrs of the insult and continue for > or =72 hrs. We report on a baby with HI who underwent therapeutic hypothermia that was initiated with a cooling fan, as the whole-body cooling machine was in use for another patient. Although overcooling occurred, the method was successful. For effective and safe brain hypothermic therapy (BHT), a purpose-built cooling machine is recommended. The adherence to standard protocol is required for every BHT, as clearly defined by protocols similar to those used in published trials.

Iatrogenic Esophageal Perforation: An Occurrence from Feeding Tube Placement in a Premature Infant with a Pneumothorax

Spontaneous neonatal esophageal perforation (EP) is a rare condition. However, iatrogenic EP due to a feeding tube is not uncommon, particularly in premature infants. Iatrogenic EP can result in serious complications, such as a pneumothorax, and can be fatal. Usually a pneumothorax develops as a result of EP. However, we experienced an EP in a patient with a pneumothorax. The EP occurred after inserting a feeding tube while the patient was suffering from a pneumothorax. Thus care is needed when inserting the feeding tube in a patient with a pneumothorax.

Successful Opening of Ductus Arteriosus with Milrinone in a Newborn with Tetralogy of Fallot and Pulmonary Atresia

Tetralogy of Fallot (TOF) assumes its' most severe form when accompanied by pulmonary atresia (PA). Preserving the patent ductus arteriosus to maintain pulmonary blood flow is life-saving for patients with this congenital heart disease. Milrinone, a selective phosphodiesterase III inhibitor, is a potent vasodilator. Here, we report the successful use of milrinone for a newborn infant with TOF and PA for keeping the ductus arteriosus open and thereby maintaining pulmonary circulation. Milrinone is a useful drug because of its inotropic, lusitropic, and pulmonary vasodilating effects, in addition to its ability to keep the ductus arteriosus open and its relatively mild side-effects. Case series and comparative studies will be needed in the future to verify the effectiveness of this drug.