Delivery mode and perinatal antibiotics influence gut microbiome composition in children. Most microbiome studies have used the sequencing of the bacterial 16S marker gene but have not reported the metabolic function of the gut microbiome, which may mediate biological effects on the host. Here, we used the PICRUSt2 bioinformatics tool to predict the functional profiles of the gut microbiome based on 16S sequencing in two child cohorts. Both Caesarean section and perinatal antibiotics markedly influenced the functional profiles of the gut microbiome at the age of 1 year. In machine learning analysis, bacterial fatty acid, phospholipid, and biotin biosynthesis were the most important pathways that differed according to delivery mode. Proteinogenic amino acid biosynthesis, carbohydrate degradation, pyrimidine deoxyribonucleotide and biotin biosynthesis were the most important pathways differing according to antibiotic exposure. Our study shows that both Caesarean section and perinatal antibiotics markedly influence the predicted metabolic profiles of the gut microbiome at the age of 1 year.

The mechanism by which cranberry-lingonberry juice (CLJ) prevents urinary tract infections (UTI) in children remains unknown. We hypothesized that it alters the composition of the gut or urinary microbiome. Altogether, 113 children with UTIs were randomly allocated to drink either CLJ or a placebo juice for 6 months. We collected urinary samples at 3 months and fecal samples at 3, 6 and 12 months and used next-generation sequencing of the bacterial 16S gene. The children who consumed CLJ had a lower abundance of Proteobacteria (p = 0.03) and a higher abundance of Firmicutes phylum (p = 0.04) in their urinary microbiome at 3 months than did those in the placebo group. The abundance of Escherichia coli in the urinary microbiome was 6% in the CLJ group and 13% in the placebo group (p = 0.42). In the gut microbiome the abundance of Actinobacteria at 3 and 12 months was higher in the children receiving CLJ. The diversity of the urinary and gut microbiome did not differ between the groups. The children drinking CLJ had a different urinary and gut microbiome from those receiving a placebo juice. A healthy urinary microbiome may be important in preventing UTIs in children.

Context: The incidence of urinary tract infection (UTI) varies with age, but there is limited evidence on the role of other risk factors. Objective: The aim of this meta-analysis was to investigate the risk factors for UTIs in children. Data sources: PubMed from 1966 to May 2019. Study selection: All studies assessing at least 1 possible risk factor for occurrence or recurrence of UTI with a clear definition of symptomatic UTI in children were eligible. We excluded studies with UTIs related to hospital treatment or severe congenital renal abnormalities. Data extraction: After the quality assessment we extracted data on the given risk factor in children with and without UTI. The data were extracted separately for the occurrence and recurrence of UTIs. Results: We included 24 studies in the meta-analysis. Circumcision decreased the occurrence of UTIs with an odds ratio (OR) of 0.1 [95% confidence interval (CI): 0.06–0.17) and breast-feeding with an OR of 0.4 (CI: 0.19–0.86), both with low heterogeneity. Being overweight or obese increased the risk of UTI (OR: 2.23; CI: 1.37–3.63). Both poor fluid intake (OR: 6.39; CI: 3.07–13.39) and infrequent voiding (OR: 3.54; CI: 1.68–7.46) were associated with recurrent UTIs. Limitations: The design, populations and definitions varied between the studies. Conclusions: Being overweight or obese and having poor fluid intake are modifiable risk factors that increase the risk for UTIs in children. Breast-feeding and circumcision are associated with a decreased occurrence of UTIs.

Some cohort studies have suggested that gut microbiota composition is associated with allergic diseases in children. The microbiota of the first‐pass meconium, which forms before birth, represents the first gut microbiota that is easily available for research and little is known about any relationship with allergic disease development.

Background: Surgical resection has proven to be the most effective long-term treatment in managing airway stenoses and has shown to decrease the risk of tumor recurrence and mortality in patients with tumor infiltration to the airways. However, there are only a few Nordic reports on the results of a tracheal resection (TR) and cricotracheal resection (CTR). This study aimed to evaluate the volume and short-term outcome of TR and CTR at our institution. Methods: Retrospective review of patients who underwent TR or CTR between 2004 and 2019 at the Results: Forty-four patients were included, of which 21 (47.7%) underwent surgery for a tumor, whereas 23 (52.3%) were operated for a benign stenosis. The most common tumor type was thyroid carcinoma with tracheal invasion (15.9%). The distance between the upper margin of the stenosis or tumor infiltration and the vocal cords was in median 3 [interquartile range (IQR), 2???5] cm and the median length of resection 2.5 (IQR, 2???3.5) cm. Overall success rate was 75% (no need for reoperation or postoperative intervention). Complications occurred in 20 (45.5%) patients, of which 10 patients were operated for a tumor, and 10 for a benign stenosis. Conclusions: Tracheal and CTRs were effective in treating tracheal and subglottic stenoses with variable etiology. However, complications were common especially following cricotracheal tumor resections. These procedures show a clear need for further centralization due to their complex nature and should therefore be performed primarily at institutes with highly experienced multi-professional teams.

BACKGROUND:Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota.METHODS:This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples.RESULTS:Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants).CONCLUSIONS:Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota.IMPACT:Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant's gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

•Robotic-assisted thoracoscopic lung lobectomy can be implemented safely and efficiently in an expert center with earlier experience in VATS lobectomies.•There seems to be a learning curve of its own despite the surgeon's previous experience in conventional thoracoscopic surgery.

Vertical transmission of maternal microbes is a major route for establishing the gut microbiome in newborns. The impact of perinatal antibiotics on vertical transmission of microbes and antimicrobial resistance is not well understood. Using a metagenomic approach, we analyzed the fecal samples from mothers and vaginally delivered infants from a control group (10 pairs) and a treatment group (10 pairs) receiving perinatal antibiotics. Antibiotic-usage had a significant impact on the main source of inoculum in the gut microbiome of newborns. The control group had significantly more species transmitted from mothers to infants (P = .03) than the antibiotic-treated group. Approximately 72% of the gut microbial population of infants at 3-7 days after birth in the control group was transmitted from their mothers, versus only 25% in the antibiotic-treated group. In conclusion, perinatal antibiotics markedly disturbed vertical transmission and changed the source of gut colonization towards horizontal transfer from the environment to the infants.

RESEARCH QUESTION:Is the growth of term singletons born after frozen embryo transfer (FET) comparable to those born after fresh embryo transfer and natural conception up to 5 years of age? DESIGN:Observational cohort study in an academic medical centre and municipal child health clinics with repeated measurements carried out by medical professionals. Term singletons born after FET (n = 110) and fresh embryo transfer (n = 181) and their matched natural conception controls (n = 543) born in Oulu, Northern Finland, were included. Mean weights, lengths, heights and head circumferences at the ages of 4, 8 and 18 months and 3 and 5 years were compared. At 3 and 5 years, body mass indices were compared. RESULTS:Childhood growth did not differ between term singletons born after FET, fresh embryo transfer and natural conception, correcting for exact age at measurement and adjusting for maternal body mass index and paternal height. CONCLUSIONS:Similar growth between children born after FET, fresh embryo transfer and natural conception offers reassurance of the safety and feasibility of the steadily increasing use of embryo cryopreservation in assisted reproduction.

Suomi seuraavan sukupolven kasvuympäristönä -raportissa kuvataan Suomessa vuonna 1997 syntyneen ikäluokan lapsia, joiden vanhemmista toinen tai molemmat ovat syntyneet ulkomailla. Lasten elämänkulkua seurataan syntymästä täysi-ikäisyyteen asti ryhmissä, jotka perustuvat vanhempien syntymävaltioon. Raportissa tarkastellaan lasten vanhempien sosioekonomista asemaa, terveyttä ja perhesuhteita. Lasten hyvinvointia tutkitaan usealla ulottuvuudella: koulutus, somaattinen ja psyykkinen terveys, lastensuojelu ja rikollisuus. Lisäksi tutkitaan lasten asuinpaikkojen alueellista jakautumista kaupunki–maaseutu-ulottuvuudella ja maakunnittain sekä lasten asuinalueiden piirteitä. Tutkimusaineistona on käytetty Terveyden ja hyvinvoinnin laitoksen Kansallinen syntymäkohortti 1997 -tutkimusaineistoa, johon on kerätty useita eri rekisteritietoja kaikista Suomessa vuonna 1997 syntyneistä henkilöistä sikiöajalta täysi-ikäisyyteen. Raportti on jatkoa aiemmalle samaan aineistoon perustuvalle seurantatutkimukselle, jonka tutkimuskohteena oli muutoin koko vuonna 1997 syntynyt ikäluokka mutta eivät erikseen ulkomailla syntyneiden vanhempien lapset. Suomessa vuonna 1997 syntyneistä lapsista 5,2 prosentilla toinen vanhemmista ja 1,7 prosentilla molemmat vanhemmat ovat syntyneet ulkomailla. Tulosten mukaan suurin osa ikäluokan lapsista voi hyvin riippumatta siitä, ovatko heidän vanhempansa syntyneet Suomessa vai ulkomailla. Kaikki ikäluokan lapset eivät kuitenkaan nauttineet samassa määrin ikäluokalle tavanomaisesta myönteisestä kasvuympäristöstä ja kehityksestä. Tulos koskee sekä Suomessa syntyneiden vanhempien lapsia että lapsia, joiden vanhemmista toinen tai molemmat ovat syntyneet ulkomailla. Osalla vanhemmista arkea kuormittivat vanhempien matala koulutustaso, toimeentulo-ongelmat sekä terveysongelmat. Joillain nuorista peruskoulu sujui heikosti ja koulutuspolku katkesi peruskoulun jälkeen. Osalla lapsista mielenterveyden ja käyttäytymisen ongelmia tai kasvuympäristön ja kehityksen vaarantavia tekijöitä pyrittiin hoitamaan erikoissairaanhoidon ja lastensuojelupalveluiden avulla. Ulkomailla syntyneiden vanhempien lapset kuitenkin erosivat jossain määrin Suomessa syntyneiden vanhempien lapsista, kun tarkasteltavana olivat edellä kuvatut asiat ja palvelut. Eroja oli sen mukaan, onko vanhemmista toinen vai molemmat syntyneet ulkomailla, sekä sen mukaan, missä maassa vanhemmat ovat syntyneet. Yhteistä koko ikäluokalle oli, että vanhemmuutta kuormittavat tekijät, kuten vanhempien toimeentulovaikeudet, olivat yhteydessä lapselle haitallisiin kehityskulkuihin. Lapset, joiden vanhemmista toinen tai molemmat ovat syntyneet ulkomailla, asuivat tyypillisemmin kaupunkialueella ja maakunnista Uudellamaalla kuin Suomessa syntyneiden vanhempien lapset. Raportin johtopäätöksissä pohditaan hyvinvointipoliittisia toimia, joilla voidaan edistää ulkomailla syntyneiden vanhempien ja heidän lastensa sosiaalista ja taloudellista hyvinvointia ja koulutusta sekä sosiaali- ja terveyspalveluiden vaikuttavuutta.

Background Recent studies have shown a diverse microbiome in the first stool after birth. The clinical significance of the microbiome of the first stool is not known. Infantile colic has earlier been associated with the composition of the intestinal microbiome. Methods We set out to test whether the microbiome of the first stool is associated with subsequent infantile colic in a prospective, population-based cohort study of 212 consecutive newborn infants. We used next-generation sequencing of the bacterial 16S rRNA gene. Results The newborns who later developed infantile colic ( n = 19) had a lower relative abundance of the genus Lactobacillus and the phylum Firmicutes in the first stool than those who remained healthy ( n = 139). By using all microbiome data, random forest algorithm classified newborn with subsequent colic and those who remained healthy with area under the curve of 0.66 (SD 0.03) as compared to that of shuffled samples ( P value <0.001). Conclusions In this prospective, population-based study, the microbiome of the first-pass meconium was associated with subsequent infantile colic. Our results suggest that the pathogenesis of infantile colic is closely related to the intestinal microbiome at birth.

SummaryBackgroundSeveral reports have revealed that the first‐pass meconium hosts a diverse microbiome, but its clinical significance is not known.ObjectiveWe designed a prospective population‐based cohort study to evaluate whether the meconium microbiome predicts subsequent growth in children.MethodsThe study comprised 212 consecutive newborns with a meconium sample and a follow‐up sample at 1 year of age. Trained nurses measured the children for weight and length using standardized techniques. We used next‐generation sequencing of bacterial 16S rRNA gene and machine‐learning approach for the analysis.ResultsThe children with overweight at 3 years of age differed in their meconium microbiome from those with normal weight, having a higher proportion of Bacteroidetes phylum (29% vs 15%, P = .013). Using the machine‐learning approach, the gut microbiome at birth predicted subsequent overweight with area under the curve 0.70 (SD 0.04). A lower proportion of Staphylococcus at birth was associated with greater length/height at 1 year (ß = −.68, P = .029) and 2 years of age (β = −.74, P = .030).ConclusionsThe microbiome of the first‐pass meconium predicted subsequent overweight at the age of 3 years. The association between the gut microbiome and overweight appears to start already during pregnancy and at birth.

Diffuse malignant mesothelioma (DMM) of the pleura is a rare and aggressive disease, wherein the long-term survival (LTS) rate is low. The epithelioid subtype is the most prevalent form of DMM with the best prognosis. To study prognostic histopathologic factors associated with extended survival in epithelioid DMM, we examined 43 tumors from patients with survival more than five years (LTSs) and compared the findings with 84 tumors from a reference group (RG) with average survival. We analyzed the tumors considering previously published histopathological prognostic features and attempted to identify additional morphological features predictive of extended survival. Most of the LTS tumors presented with nuclear grade I (n = 34, 90%) and a tubulopapillary growth pattern (n = 30, 70%). One LTS tumor had necrosis. In contrast, nuclear grade II (n = 49, 61%) and solid growth pattern (n = 59, 70%) were more frequent in the RG, and necrosis was present in 16 (19%) tumors. We also evaluated the association of asbestos lung tissue fiber burden quantified from autopsy samples with histopathological features and found that elevated asbestos fiber was associated with higher nuclear grade (P < 0.001) and the presence of necrosis (P = 0.021). In univariate survival analysis, we identified the following three novel morphological features associated with survival: exophytic polypoid growth pattern, tumor density, and single mesothelium layered tubular structures. After adjustments, low nuclear grade (P < 0.001) and presence of exophytic polypoid growth (P = 0.024) were associated with prolonged survival. These results may aid in estimating DMM prognosis.

INTRODUCTION:Malignant pleural mesothelioma (MPM) is a fatal malignancy strongly associated with previous asbestos exposure. Overall survival remains dismal, partly owing to poor response to available treatment. The aims of this study were to evaluate diagnostic accuracy in a group of patients with MPM with an unusually long survival time and to assess the factors related to this prolonged survival.MATERIALS AND METHODS:Forty-three patients with overall survival exceeding 5 years were accepted to the long-term survivor (LTS) group, and these patients were compared with 84 patients with epithelial MPM. Data were collected from various national registries and electronic medical records. In addition, all available histopathologic diagnostic samples and computed tomography studies were re-evaluated by experienced specialists.RESULTS:Our study showed a good diagnostic accuracy, with only 1 (0.5%) patient having an incorrect MPM diagnosis. Two (0.9%) localized malignant mesotheliomas and 2 (0.9%) well-differentiated papillary mesotheliomas were also found. LTS patients were younger, more frequently female, had a better performance status at time of diagnosis, and had less evidence of prior asbestos exposure. In multivariate analysis, we showed tumor size, Eastern Cooperative Oncology Group performance status, and first-line treatment (both surgery and chemotherapy) to be associated with survival time.CONCLUSION:We confirmed the diagnosis of MPM in an overwhelming majority of patients in the LTS group. An epithelial subtype of MPM behaving clinically more indolently seems to exist, but further tumor and genetic characterization is needed. The prolonged survival time is most likely explained by a combination of tumor-, patient-, and treatment-related factors.

Malignant peritoneal mesothelioma (MPeM) is a rare cancer of the mesothelial cells of the peritoneum. Computed tomography (CT) is considered the standard for first-line imaging of MPeM, diagnosis and risk stratification remains challenging. Peritoneal cancer index (PCI), as assessed by CT, is utilized in the prognostic assessment of other malignant intra-abdominal conditions; however, there is limited data concerning the utility of PCI in the diagnosis and workup of MPeM. We studied a retrospective cohort of all patients diagnosed with MPeM from 2000 to 2012 in Finland. CT and magnetic resonance imaging (MRI) were reviewed and scored by an experienced and blinded, board-certified abdominal radiologist. Additional clinical data and outcomes were obtained from Finnish Cancer Registry (FCR), the Workers’ Compensations Center (WCC), and Statistics Finland (SF). Abdominal CT or MRI was available for 53 of 90 patients. The median radiographic PCI was 25. PCI score was correlated with overall survival ( p = 0.004, Exp(B) = 1.064, 95% CI 1.020–1.110). PCI score ≥ 30 was associated with worse survival ( p = 0.002), while PCI ≤ 19 was associated with improved overall survival ( p = 0.001). Our study indicates that radiological PCI is prognostic in MPeM and should be assessed during radiographic workup and integrated into clinical decision-making.

BACKGROUND:Malignant peritoneal mesothelioma (MPeM) is a rare type of cancer with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival. Treatment and survival of patients with MPeM have not been previously studied in Finland.MATERIALS AND METHODS:The data consisted of all patients diagnosed with MPeM during years 2000-2012 in Finland, including cancer notifications, death certificates and information about asbestos exposure.RESULTS:Among 50/94 (53.2%) patients treated for MPeM, 44/50 (88.0%) were treated palliatively, 4/50 (8.0%) with radical surgery and chemotherapy, and 2/50 (4.0%) with CRS plus HIPEC. Five-year survival was 50.0% for those treated with CRS plus HIPEC and 75.0% for those treated with radical surgery and chemotherapy. Radical surgery with chemotherapy was associated with significantly longer survival compared to radiation (p=0.008), chemotherapy and radiation (p=0.043), surgery, chemotherapy and radiation (p=0.039), and palliative surgery (p=0.009).CONCLUSION:Treatment of MPeM is heterogenic in Finland. CRS plus HIPEC, and radical surgery with chemotherapy seem to increase the survival. Patients considered candidates for radical surgery should be sent to specialized centers for further assessment.

BACKGROUND:As a result of routine low-dose computed tomographic screening, lung cancer is more frequently diagnosed at earlier, operable stages of disease. In treating local non-small-cell lung cancer, video-assisted thoracoscopic surgery (VATS), a minimally invasive surgical approach, has replaced thoracotomy as the standard of care. While short-term quality-of-life outcomes favor the use of VATS, the impact of VATS on long-term health-related quality of life (HRQoL) is unknown. PATIENTS AND METHODS:We studied patients who underwent lobectomy for the treatment of non-small-cell lung cancer from January 2006 to January 2013 at a single institution (n = 456). Patients who underwent segmentectomy (n = 27), who received neoadjuvant therapy (n = 13), or who were found to have clinical stage > T2 or > N0 disease (n = 45) were excluded from analysis. At time of HRQoL assessment, 199 patients were eligible for study and were mailed the generic HRQoL instrument 15D. RESULTS:A total of 180 patients (90.5%) replied; 92 respondents underwent VATS while 88 underwent open thoracotomy. The VATS group more often had adenocarcinoma (P = .006), and lymph node stations were sampled to a lesser extent (P = .004); additionally, hospital length of stay was shorter among patients undergoing VATS (P = .001). No other clinical or pathologic differences were observed between the 2 groups. Surprisingly, patients who underwent VATS scored significantly lower on HRQoL on the dimensions of breathing, speaking, usual activities, mental function, and vitality, and they reported a lower total 15D score, which reflects overall quality of life (P < .05). CONCLUSION:In contrast to earlier short-term reports, long-term quality-of-life measures are worse among patients who underwent VATS compared to thoracotomy.

Background and aims: Previously, colorectal cancer (CRC) metastasis of both liver and lungs was considered disseminated disease, which contraindicated surgical metastasectomies. Increasing evidence from studies on patient series have indicated that survival improved after resecting both liver and lung metastases. However, those results and long-term outcomes remain controversial. We aimed to compare surgical outcomes between patients treated for both liver and lung metastases to the patients who had only isolated liver or lung metastases. Material and methods: All patients (n = 105) underwent surgery for CRC metastases between July 2002 and September 2015. Three groups were compared: the sequentially operated group (n = 33 patients) underwent sequential liver and lung resections; the liver group (n = 38 patients) underwent liver resections; and the lung group (n = 34 patients) underwent lung resections. The main endpoints were long-term survival rates. Results: The groups were not different in disease-free survival (P = 0.727) or overall survival (P = 0.218). Five-year survival rates were 69.7% in the sequentially operated group, 65.1% in the liver group, and 50.0% in the lung group. Conclusion: Long-term outcomes after sequential liver and lung resections of CRC metastases were comparable to outcomes after isolated liver or lung metastasectomies. Therefore, aggressive surgical interventions should be considered for patients with both liver and lung metastases of CRC.

Objective: Clinical T2N0 esophageal carcinoma is a heterogenous disease frequently complicated by inaccurate staging. Incorrect staging may lead to sub-optimal treatment for patients with unidentified local-regionally advanced disease. Therapeutic options for these patients remain controversial. We sought to evaluate the outcomes of patients with cT2N0 who underwent esophagectomy as either primary therapy or after neoadjuvant treatment. Methods: This was a multi-institutional collaboration of 26 high-volume esophageal centers. Patients with complete staging who underwent elective resection from 2002 to 2012 were included. Three treatment groups were identified; primary esophagectomy, preoperative chemotherapy, and preoperative chemoradiation (CXRT). Pretreatment variables were explored for independent predictors of long-term outcomes. The primary esophagectomy subgroup was evaluated for stage migration. Results: In total, 767 patients were evaluated; 35%(268) had preoperative therapy (195 CXRT, 73 chemotherapy). Staging accuracy was 14%(70/499), with pT<2 identified in 45%(222) and pN>0 in 39%(195). Preoperative treatmentmodality (none, CXRT, chemotherapy) was not identified as a predictor of outcome (median survival 63, 70, 71 months, respectively, P =.956). Longitudinal tumor length > 3.25 cm was predictive of pNthorn for the primary esophagectomy cohort as well as adenocarcinoma histology only (odds ratio 2.2 and 2.4, respectively, P<. 001). Conclusions: Current treatment options for patients with cT2N0M0 do not reveal a comparative survival advantage to preoperative therapy. Pretreatment tumor length can identify a subgroup of patients at risk for understaging (pNthorn). The incidence of overstaging suggests that organ-sparing approaches (endoscopic resection) may play a future role in appropriately selected patients.