Twenty years' experience of midgut malrotation and volvulus in a tertiary center in northern Taiwan: A retrospective study.

BACKGROUND: Early diagnosis and surgical intervention for midgut malrotation with bowel obstruction are crucial. We aimed to identify risk factors for adverse outcomes in infants with midgut malrotation and to develop a prediction model. METHODS: We reviewed the operation records of infants surgically diagnosed with midgut malrotation at Chang Gung Children's Medical Center between January 2000 and December 2020. Patients were classified into the poor-outcome group (PO) if they underwent bowel resection or experienced mortality; all others were categorized as the favorable-outcome group (FO). Data on demographics, initial presentations, laboratory results, radiographic or sonographic findings, maternal conditions, and outcomes were collected and analyzed. Fisher's exact test, the independent sample t-test, and the Mann-Whitney test were utilized for comparative analysis when suitable. RESULTS: The study included 103 infants. Eleven were in the PO group, and 92 were in the FO group. Initial presentations such as respiratory distress, poor activity, and shock status were notably more prevalent in the PO group. The INR, hemoglobin, HCO3, base excess, and aspartate transaminase values showed significant variation between the two groups. Multivariate analysis identified that lower hemoglobin (OR 0.677, p = 0.043) and higher AST (OR 1.036, p = 0.044) were independent predictors of adverse outcomes. An AST/Hb ratio of <3.78 demonstrated a high negative predictive value (98.6%) for an adverse outcome in midgut malrotation. CONCLUSIONS: Prompt diagnosis and surgical treatment of midgut malrotation are vital to prevent bowel resection or mortality. The independent predicting factors for poor outcomes include low hemoglobin and elevated AST levels.

Lung adenocarcinoma with EGFR L858R-K860I and L858R-L861F doublet mutations from which the L858R mutation is undetectable through the cobas EGFR mutation test v2.

In East Asia, epidermal growth receptor factor (EGFR) mutations are the most prevalent and important biomarkers for treating patients with advanced lung cancer. However, as L858R doublet mutations are rare, commercially available EGFR tests may yield false-negative results. To determine whether the L858R mutation of the L858R-K860I and L858R-L861F doublet mutations could be identified using different types of EGFR detection tests and to describe the clinical response of patients with lung cancer with L858R doublet mutations to EGFR tyrosine kinase inhibitors (TKI). Information and samples from four patients with L858R doublet mutations, including three with L858R-K860I and one with L858R-L861F, were retrospectively collected from the archives of our department. For each case, the clinical response to EGFR-TKI was retrieved from the medical records. Archived formalin-fixed paraffin-embedded blocks were subjected to Sanger sequencing, the cobas and Idylla EGFR tests, the IntelliPlex-LCP-DNA assay, and AmoyDx PLC panel. L858R mutations were all detected by Sanger sequencing and the Idylla EGFR test but missed by the cobas assay. The AmoyDx PLC detected L858R only in cases with L858R-K860I while the IntelliPlex-LCP-DNA assay detected L858R in the case with L858R-L861F. Additionally, three of the patients, who had measurable tumors, showed partial responses to afatinib and osimertinib. The L858R mutation associated with L858R-K860I and L858R-L861F doublet mutations could be detected using Idylla but not cobas EGFR tests. Using next-generation sequencing analysis should be considered after initial negative reports from the cobas test, because patients with L858R doublet mutations may benefit from EGFR-TKIs.

The trends of pediatric duodenal ulcer and predictors of recurrence.

BACKGROUND: Duodenal ulcer (DU) causes various symptoms in children. The prevalence of Helicobacter pylori (Hp)-associated DU has been reducing in some regions, yet the updated trend in Taiwan is unknown. Risk factors of DU recurrence have not been comprehensively investigated in children. METHODS: This retrospective study included children diagnosed with DU to evaluate the demographics, symptoms, diagnostics, treatment, and outcomes. Specific populations (infant, surgery required) were sorted for subgroup analysis. Predictors of DU recurrence was analyzed in patients who received endoscopic follow-ups. RESULTS: A total of 488 children were included. Most patients were male (72.5%), school-aged (11.3 ± 4.8 years old), and with varied underlying diseases in one-fifth. The annual incidences were around 3-5%, with a declining trend of case numbers and the Hp-positive proportion. Hp infection, concurrent gastric ulcer, perforation, and mortality were noted in 32.7%, 16%, 1.6%, and 1% of patients. Patients with or without Hp infection showed different clinical features but similar outcomes. The characteristics of subpopulations were depicted respectively. Male sex, lower Hb level, and perforation were independent risk factors associated with recurrence. CONCLUSIONS: Hp-positive DU seems to wane. Patients with male sex, lower Hb level, or perforation at diagnosis carried a higher risk of recurrence, which may warrant active surveillance and endoscopic follow-up.

A case series and literature review on 98 pediatric patients of germ cell tumor developing growing teratoma syndrome.

INTRODUCTION: Malignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on the clinical characteristics and outcomes of GTS in children with MGCTs are limited. METHODS: We retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS. RESULTS: The sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety-five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event-free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5-year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001). CONCLUSION: For patients with high-risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.

Clinical characteristics of pediatric intussusception and predictors of bowel resection in affected patients.

Background: Surgery is required for the treatment of intussusception when enema reduction is unsuccessful, or when the patient develops peritonitis, bowel perforation, or intestinal damage. We aimed to evaluate the clinical and laboratory parameters that may be used to predict the need for bowel resection in children with intussusception. Methods: This observational retrospective study included children who were admitted to the pediatric emergency department with intussusception. Univariate and multivariate logistic regression models were used to evaluate factors associated with bowel resection. Results: In total, 584 children with intussusception were admitted to the pediatric emergency department; 129 of these children underwent surgery. Multivariate analysis revealed the following independent predictors of bowel resection for intussusception: symptoms for at least 2 days before surgery (OR = 6.863; p = 0.009), long intussusception (OR = 5.088; p = 0.014), pathological lead point (OR = 6.926; p = 0.003), and intensive care unit admission (OR = 11.777; p = 0.001) were factors independently associated with bowel resection. Conclusion: Symptoms for at least 2 days before surgery, long intussusception, pathological lead, and intensive care unit admission were predictors of bowel resection in children with intussusception. These findings can be used to identify patients at high risk of needing surgery and bowel resection.

Malignant testicular tumors in children: A single institution's 12-year experience.

Testicular neoplasms are not commonly found in children and are a formidable threat if treated inappropriately. However, there is no consensus regarding its management. This study aimed to create a holistic picture of the interprofessional team in the management of malignant testicular tumors. Seventeen patients had mixed germ cell tumors, 15 had pure yolk sac tumors, 2 had immature teratomas, 2 had teratocarcinomas, and 1 had a sex cord stromal tumor. Five lesions were diagnosed as nongerm cell tumors: 2 embryonal rhabdomyosarcomas, 2 lymphomas, and 1 acute myeloid leukemia. At initial presentation, retroperitoneal (n = 2), bone marrow (n =1), and mediastinal (n = 1) metastases were identified in 4 (10%) patients. The operative interventions performed included radical inguinal orchiectomy (n = 5), scrotal orchiectomy (n = 31), and testicular biopsy or testis-sparing enucleation of the tumor (n = 6). Postoperatively, 18 patients received either adjuvant chemotherapy (n = 14) or chemoradiation (n = 5). Five patients with mixed germ cell tumors (n = 2), group IV paratesticular rhabdomyosarcoma (n = 2), and acute myeloid leukemia with myeloid sarcoma (n =1) died of disease progression. Thirty-six patients remained alive and disease-free at the last visit. Malignant testicular tumors in children deserve proper diagnostic support from a therapeutic perspective. Any concern or suspicion of a testicular tumor warrants an inguinal approach to avoid scrotal violation.

Characteristics and Risk Factors for Ischemic Ovary Torsion in Children.

Identifying ischemic ovary as a complication of ovary torsion (OT) is a significant challenge in children. This study identified risk factors for ischemic OT among pediatric OT patients to prevent delayed treatment. This retrospective study included pediatric inpatients who underwent operation for OT over 20 years. We employed multivariable logistic regression to find the risk factors associated with ischemic OT. Among the 118 patients included in this study, 78 (66.1%) had ischemic OT. Patients with ischemic OT tended to be younger; had more frequent vomiting; and had elevated White blood cell (WBC), C-Reactive protein (CRP), and segments in comparison with non-ischemic OT patients. Multivariable regression showed increased odds of ischemic ovary torsion, associated with higher WBC (12.3 × 103/mm3 vs. 8.7 × 103/mm3, p < 0.001), CRP (50.4 mg/L vs. 8.4 mg/L, p < 0.001), and vomiting (55.1% vs. 25%, p = 0.002) than in non-ischemic patients. A receiver-operating characteristic (ROC) analysis indicated that patients with vomiting, leukocytosis, or CRP ≧ 40 mg/L were more likely to have ischemic OT (sensitivity, 92%; specificity, 54%; PPV, 79.6; NPV, 78.9%). Ischemic OT is common among pediatric OT patients. The presence of potential risk factors of vomiting, leukocytosis, and CRP more significant than 40 mg/L may assist clinicians in ensuring an expedited surgical treatment.

Clinical Presentations, Diagnosis, and Management for Pediatric Antral Web-A 20-Year Experience of a Referral Center.

Background: Antral web is a rare cause of gastric outlet obstruction in children. The presentation is diverse, depending on the degree of obstruction. Unfortunately, the guidance of management is still lacking. Methods: This study retrospectively evaluated the presentations, management, and outcomes of the pediatric antral web based on a 20-year experience in a referral center. Results: A total of 23 cases were included. The median age of diagnosis was 10 months (interquartile range, IQR, 0.8-23 months). Main presentations comprised vomiting (83%) and upper gastrointestinal (UGI) bleeding (48%). Concurrent gastric ulcers were common (68%). A total of 13 cases (57%) underwent interventional treatment. The median duration from diagnosis to intervention (DtI) was 10 days, but five with longer DtI, ranged from 30 to 755 days. Among the 15 cases with concurrent gastric ulcers, 10 patients received intervention, immediately in six but delayed in four. Surgical treatments (N = 12) achieved a cure in 11, with one rescued by endoscopic treatment. Conclusions: Children who suffer from early gastric ulcers with outlet obstruction shall raise the suspicion of the antral web. Complete obstruction madates early intervention. Around half of the cases with adequate feeding and growth need no intervention. Recurrent obstructive symptoms or adjacent ulcers justify a switch from observation to intervention to avoid complications or growth faltering.

Patent urachus or bladder exstrophy occulta? A case of prenatally disappeared umbilical cord cyst.

We are reporting an umbilical cyst detected at early trimester which mimicking bladder exstrophy occulta. A 3-cm umbilical cord cyst and a slight ventrally located urinary bladder beneath the cord insertion site was detected at 14th gestational weeks, which decreased in size and disappeared at 28th week. A term female neonate born with a 2-cm defect over the base of the umbilical cord, revealed a patent urachal fistula, and a part of the herniated urinary bladder. Detection of a vanished umbilical cord cyst has to keep aware of, making an immediate definite diagnosis and management of urachal anomaly.

Malignant sacrococcygeal germ cell tumors in children in Taiwan: A retrospective single-center case series.

ABSTRACT: Although the incidence of malignant sacrococcygeal germ cell tumors (MSGCTs) is high in the East Asian countries, information about MSGCTs from this region is limited. This report aimed to analyze the data of children with MSGCTs in a single medical center in Taiwan.Patients aged 18 years or younger with primary MSGCTs or malignant recurrence of a sacrococcygeal teratoma who underwent surgery during the neonatal period between January 1999 and December 2016 were identified from the Linkou Chang Gung Cancer Center registry. The clinical features, laboratory data, and treatment outcomes were reviewed.Fifteen children (1 man and 15 women) with MSGCTs were identified. Sacrococcygeal tumors were present at birth in 7 patients. All patients presented with a bulging mass at the buttock region and they had normal alpha-fetoprotein levels at the time of diagnosis. They underwent primary excision of the tumor. Immature teratoma was histologically diagnosed in 5 neonates, and mature teratoma in 2. Only 1 patient with grade 3 immature teratoma received adjuvant chemotherapy. Two patients with mature teratoma developed malignant recurrence 1.6 and 2.1 years later, respectively. Eight patients were diagnosed with MSGCTs after the neonatal period. The common presenting symptoms included buttock asymmetry (37.5%), abdominal distension (25%), and constipation (12.5%). Seven patients had elevated alpha-fetoprotein levels for their age. They were administered neoadjuvant chemotherapy followed by tumor excision if a residual tumor was present. The histology of the excised tumor included mature teratoma (66.7%) and necrosis (33.3%). One patient with a normal alpha-fetoprotein level underwent primary tumor excision followed by adjuvant chemotherapy. Grade 2 immature teratoma with embryonal carcinoma was diagnosed histologically. Among the 15 patients with MSGCTs, 3 had a recurrence (at age of 2.1, 0.5, and 2.4 years, respectively) and 1 died (at age of 6.1 years) of disease progression. The 5-year overall and event-free survival rates were 90% and 80%, respectively.Children with MSGCTs had good overall prognoses in this case series. For those with sacrococcygeal mature teratoma or low-grade immature teratoma in the neonatal period, we recommend close follow-up for at least 3 years after surgery to detect malignant recurrence.

High initial bowel resection rate and very-early-onset inflammatory bowel disease - A challenge in a low-prevalence area.

BACKGROUND: Inflammatory bowel diseases (IBD) include ulcerative colitis (UC) and Crohn's disease (CD). The incidence in children and adolescents has risen since the 21st century globally, including Taiwan. The study aimed to disclose the characteristics and outcome of pediatric IBD (pIBD) patients in a tertiary center for the past two decades. METHODS: We retrospectively reviewed the charts of pIBD children from 2000 to 2018 in a tertiary center in Northern Taiwan. Demographics, presentations, diagnostic modalities, treatment, and outcomes were analyzed. RESULTS: A total of 38 cases were enrolled, including 27 CD and 11 UC patients. An almost 3-folds increase in incidence after 2010 was observed. Twelve cases (32%) were early-onset, and six of them (16%) were very-early-onset; four of them were detected with single-gene mutations [XIAP, TTC7A (2 siblings), and ZAP70]. Eleven CD patients (40.7%) received bowel resection at the onset, and another two (7.4%) had bowel resection years after the diagnosis. Initial bowel resection was associated with fibrostenotic/penetrating behavior, early-onset disease, and growth failure. CONCLUSION: This study demonstrated an increased incidence of pIBD in the past two decades in Taiwan, a low-prevalence region. The initial high bowel resection rate in CD was related to the fibrostenotic and/or penetrating behavior, younger age at diagnosis, and growth failure.

Rare Cases of Pediatric Vasoactive Intestinal Peptide Secreting Tumor With Literature Review: A Challenging Etiology of Chronic Diarrhea.

Vasoactive intestinal peptide (VIP) secreting tumor (VIPoma) is a rare disease, presenting with profuse diarrhea, electrolyte imbalance, and possibly fatal outcome. The diagnosis and treatment are challenging, and no consensus guideline of management is available. The pediatric incidence remains unclear. This study comprises two pediatric case reports from a tertiary center and a literature-based case series investigating the characteristics among children. The two reported cases both presented with severe diarrhea and laboratory abnormalities, including electrolyte imbalance and elevated plasma VIP level. Case 1 received several imaging investigations, partial pancreatectomy, octreotide, and everolimus, reflecting her complicated and refractory course. Case 2 underwent total excision of suprarenal ganglioneuroblastoma, and the clinical response was significant. In both cases, varied degrees of symptomatic control, reduced plasma VIP level, and correction of electrolyte imbalance were achieved. A literature review-based case series analyzed 45 pediatric cases retrieved from the PubMed database until December 31, 2019. Demographics, clinical features, diagnostic modalities, treatments, and outcomes were presented.

Distinctive genetic variation of long-segment Hirschsprung's disease in Taiwan.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital disorder with the absence of myenteric and submucosal ganglion cells within distal gut. Due to multigenic inheritance and interactions, we employed next-generation sequencing (NGS) to investigate genetic backgrounds of long-segment HSCR (L-HSCR) in Taiwan. METHODS: Genomic DNA extracted from peripheral blood of L-HSCR patients was subjected to capture-based NGS, based on a 31-gene panel. The variants with allele frequency <0.05 and predicted by computational methods as deleterious were further validated by Sanger sequencing in patients and their family as well to tell de novo from inherited variants. RESULTS: Between 2015/04 and 2018/05, this study enrolled 23 L-HSCR patients, including 15 (65.2%) sporadic cases and 8 (34.8%) familial patients in 4 different families. Six sporadic and seven familial cases showed possible harmful variants across eight different genes, accounting for an overall detection rate of 56.5%. These variants mainly resided in SEMA3C, followed by RET, NRG1, and NTRK1. Three sporadic and 2 familial cases exhibited strong pathogenic variants as a deletional frameshift or stop codon in RET, L1CAM or NRG1. In a HSCR family, the father passed on a pathogenic RET frameshift to two daughters; however, only one developed HSCR. CONCLUSION: Using NGS, we disclosed deleterious mutations such as a frameshift or stop codon in either familial or sporadic patients. Our cases with isolated L-HSCR or even total colonic aganglionosis appeared to exhibit complex patterns of inheritance and incomplete penetrance even in families with the same genetic variants, reflecting the possible effects of environmental factors and genetic modifiers.

Unilateral renal artery stenosis presented with hyponatremic-hypertensive syndrome - case report and literature review.

BACKGROUND: Renal artery stenosis is one of the secondary causes of pediatric hypertension. Cases with critical unilateral renal artery stenosis manifesting with the hyponatremic hypertensive syndrome are rare and a comprehensive description of this disorder in the pediatric population is lacking in the literature. CASE PRESENTATION: We describe a 4-year-old boy who presented with severe hypertension, profound hyponatremia, hypokalemia, nephrotic range proteinuria, and polyuria. Distinctly, the diagnosis of hyponatremic hypertensive syndrome secondary to unilateral renal artery stenosis was confirmed in light of laboratory and radiographic findings of severe natriuresis, elevated renin, and unilateral small kidney. Two weeks following nephrectomy, there was resolution of hyponatremia, hypokalemia, nephrotic range proteinuria and hypertension. CONCLUSIONS: Findings of hyponatremia, hypokalemia, hypertension, polyuria, and unilateral renal hypoplasia can be attributed to a unifying pathology of unilateral renal artery stenosis.

Fixation of lung apex in spontaneous pneumothorax is safe and efficient in decrease recurrences.

BACKGROUND: Video-assisted thoracoscopic bullectomy with pleurodesis is widely used to treat spontaneous pneumothorax. However, 1%-3% of patients experience postoperative complications that may require reoperation, such as bleeding or prolonged air leaks, and 3%-7% of patients require a repeat thoracoscopic bullectomy due to recurrence. Therefore, a modified procedure with improved outcomes is required. METHODS: Between January 1, 2011 and December 31, 2015, 196 patients with spontaneous pneumothorax underwent thoracoscopic bullectomy and pleurodesis with or without fixation of the lung apex to the chest wall. In patients in the fixation group, the lung apex was fixed to the chest wall with two non-absorbable sutures after bullectomy and pleurodesis. The treatment of each lung was considered an independent operation in patients with bilateral spontaneous pneumothorax. RESULTS: The patients in each group had comparable backgrounds. In the fixation group, 67 patients underwent 87 operations, four of which (in three patients) led to recurrences (recurrence rate, 4.60%). There were no readmissions or reoperations within 30 days in this group. In the non-fixation group, 128 patients underwent 161 operations, 14 of which (in nine patients) led to recurrences (recurrence rate, 8.7%). In addition, three patients in this group required reoperation and two were readmitted within 30 days. CONCLUSIONS: Modified thoracoscopic bullectomy with fixation of the lung apex is a safe procedure that provides better outcomes with lower complication rates.

An Age-Stratified Longitudinal Study of Primary Spontaneous Pneumothorax.

PURPOSE: The objective of this study was to determine the age-stratified incidence, frequency, and duration of recurrence of primary spontaneous pneumothorax (PSP). METHODS: This study analyzed the epidemiology of PSP among hospitalized patients using the National Health Research Institutes of Taiwan database. The incidence of PSP was determined from a cohort of 19,562 deidentified individuals with PSP between 2001 and 2013. The insurants consisted of 99% of the Taiwan population of about 23 million people. A 5- to 12-year long-term recurrence analysis was based on data from 11,190 patients with PSP between 2001 and 2008. RESULTS: The incidence of PSP in in-patients increased from 5.05 to 7.18/100,000 in a 13-year analysis. The age group at highest risk was 15-22 years with incidence rates >11/100,000 and readmission rates of 17%-31%. About 20% of patients had more than one attack based on long-term follow-ups. About .8% of patients had more than three hospital admissions. Only 3.9% of patients had repeated or recurrent attacks after more than 4 years. All patients who had been admitted on more than four occasions were adolescents, except for four patients who were aged between 20 and 24 years old. CONCLUSIONS: Adolescents with PSP had a higher incidence of attacks and more frequent and longer periods of vulnerability to recurrence. The majority of patients experienced recurrence during the first 4 years after the first attack.

Development of a gastric carcinoid tumor following allogeneic hematopoietic stem cell transplantation for early T-cell precursor acute lymphoblastic leukemia.

Gastric carcinoid tumor is rarely diagnosed in children. We report a case of gastric carcinoid tumor that occurred after allogeneic HSCT. A 13-year-old girl with ETP acute lymphoblastic leukemia underwent allogeneic HSCT from a 7/8 HLA-matched unrelated donor. She presented with rashes, abdominal pain, and diarrhea, which were suggestive of GVHD, 7 months after HSCT. Immunosuppressive agents failed to resolve these symptoms well. After a series of evaluations, carcinoid syndrome caused by a gastric carcinoid tumor was diagnosed. The tumor was located in the antral region and resulted in partial gastric outlet obstruction. She received subtotal gastrectomy with regional lymph node dissection. However, she had a flare-up of GVHD 1 month after surgery, and immunosuppressive therapy was intensified accordingly. Although her GVHD was getting better, she developed respiratory syncytial viral pneumonia with rapid progression to respiratory failure. She died of multiple organ failure 2 months postoperatively. This is the first pediatric case of a gastric carcinoid tumor following allogeneic HSCT. Our case also highlights the necessity for pediatric transplant physicians to be aware of carcinoid syndrome caused by this rare tumor in the setting of GVHD with poor response to immunosuppressive agents.

Strangulated small bowel obstruction in children.

BACKGROUND: Diagnosing intestinal strangulation as a complication of small bowel obstruction (SBO) remains a considerable challenge in children. We evaluated the clinicoradiological parameters for predicting the presence of a strangulated intestine. METHODS: We reviewed the medical records of 69 pediatric patients who underwent operation for acute SBO. Regression analysis was used to identify the parameters for predicting strangulated SBO. RESULTS: Of the 69 patients with SBO, 27 patients had intestinal strangulation and were awarded one point each towards the overall clinical score: intractable continuous abdominal pain, tachycardia, white blood cell count >13,600/mm3, and abdominal distention. Patients with a clinical score ≥2 combined with the presence of ascites in ultrasound (US) results or with wall thickness and reduced wall contrast enhancement in abdominal computed tomography (CT) scans showed strong evidence for intestinal strangulation. CONCLUSION: The combination of two or more clinical parameters, including intractable continuous abdominal pain, tachycardia, leukocytosis, and abdominal distention with the presence of ascites in US or wall thickness and reduced wall contrast enhancement in, is useful for the identification of strangulated SBO. THE TYPE OF STUDY AND LEVEL OF EVIDENCE: Prognosis study; Level III.