[Proactively embracing the challenges of multimorbidity].

With rapid socio-economic development and the acceleration of population aging, the average life span of human beings has increased significantly. Individuals suffering from the co-existence of multiple diseases (multimorbidity) have become a new normal in public health and posed severe challenge to human health. Multimorbidity significantly reduces the quality of life, increases disability and mortality risks, complicates disease treatment and care and increases burden of the healthcare system with higher costs. This commentary discusses the definition of multimorbidity and common public misconceptions, then assesses its profound impact on overall public health, socio-economic development and healthcare system. We also proposes the potential strategies to meet the challenges posed by multimorbidity. The main aim is to raise awareness of multimorbidity, advocate proactive responses to improve public health and build a healthy society through the development of prevention and treatment systems and promote precision prevention and treatment for multimorbidity.

[Abnormal changes of static and dynamic functional connectivity of dopaminergic midbrain in patients with first-episode schizophrenia and their correlations with clinical symptoms].

Objective: To investigate the abnormal changes of static functional connectivity (sFC) and dynamic functional connectivity (dFC) in the dopaminergic midbrain (ventral dorsal tegmental area and bilateral substantia nigra compacta, VTA/SNc) in patients with first-episode schizophrenia(SCH), and their correlation with the Positive and Negative Symptom Scale (PANSS). Methods: The data of 198 first-episode untreated schizophrenia patients and 199 healthy controls (HC) matched by age, sex and years of education who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2019 to May 2022 were prospectively collected. All subjects underwent high resolution structural MRI and resting state functional magnetic resonance imaging (rs-fMRI) scanning. The dopaminergic midbrain (VTA/SNc) was defined as three regions of interest (ROI). The sFC and dFC analyses with VTA/SNc as seeds were performed to produce a whole-brain diagram initially, which subsequently were compared between schizophrenia group and HC group. Finally, the correlation analysis of sFC and dFC values with the PANSS scores were performed, including the positive scale score, negative scale score, general psychopathology scale score, total score and symptom scores. Results: There were 86 males and 112 females in SCH group, and aged (23±9) years. Meanwhile, there were 95 males and 104 females in HC group, and aged (22±5) years. In the SCH group, the positive (P), the negative (N) and the general psychopathology (G) scale scores and the total score (T) of the PANSS scale was 20±7, 21±7, 41±11 and 82±22, respectively. Compared with the HC group, the VTA showed decreased sFC with four clusters including cerebellar vermis 7/9, left putamen, right thalamus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-4.35, -4.81, -4.35 and -4.65; voxel P<0.005; cluster P<0.05), the right SNc showed decreased sFC with four clusters including left cerebellar hemisphere 4/5/8, right putamen, right medial orbitofrontal gyrus and the left putamen in the schizophrenia group (peak center, t=-4.91, -5.15, -4.77 and -5.21; voxel P<0.005; cluster P<0.05), and the left SNc showed decreased sFC with four clusters including the left putamen, right putamen, right medial orbitofrontal gyrus and left middle cingulate gyrus in the schizophrenia group (peak center, t=-5.82, -4.83 and -4.65; voxel P<0.005; cluster P<0.05). Compared with the HC group, the VTA showed decreased dFC with the right inferior parietal gyrus, right angular gyrus and right superior parietal gyrus in schizophrenia group (t=-4.17). In the schizophrenia group, the sFC value of cluster 2 (left putamen) with VTA as seed and cluster 4 (left putamen) with right SNc as seed were positively correlated with the positive scale scores in PANSS (r=0.141, 0.169, both P<0.05). The sFC and dFC values of significant regions were also correlated with hallucination, delusion, suspicion, hostility, communication disorder, passivity/indifference, lack of communication, stereotyped thinking, depression, non-cooperation, lack of judgment and insight, impulse control disorder, active social avoidance (all P<0.05). Conclusion: The static and dynamic functional connectivity (stability) of VTA/SNc to cerebellum, thalamus, striatum, prefrontal lobe and cingulate gyrus in first-episode schizophrenia patients were decreased, which were closely related to the positive and negative symptoms of schizophrenia.

[Analysis of abnormal dynamic functional connectivity of the raphe nucleus in adolescent patients with first-episode depression on resting-state functional magnetic resonance imaging].

Objective: To investigate the dynamic functional connectivity (dFC) abnormalities of the raphe nucleus in adolescent patients with first-episode depression and its correlation with clinical characteristics and cognitive function. Methods: A total of 30 adolescent patients with untreated depression [Depression Groups, 17 males and 13 females, median age 16.5 (15.0, 17.0) years] and 29 age-, gender-and education-[Healthy Controls, 17 males and 12 females, median age 17.0 (16.0, 18.0) years] matched healthy controls underwent resting functional MRI examinations and their clinical data were obtained in the First Affiliated Hospital of Zhengzhou University.The raphe nuclei was subdivided into dorsal raphe nuclei (DRN) and median raphe nuclei (MRN). Seed-based dFC of the raphe nucleus was conducted to analyze the abnormal dFC between DRN and whole brain gray matter as well as MRN. Clinical characteristics and cognitive function were evaluated using HAMD-17 and Wisconsin card sorting (WSCT), respectively. The difference of dFC between the two groups was compared. The variance values of dFC in the different brain regions were extracted and subsequently used for evaluating the correlation between the scores of HAMD-17 as well as cognitive tests. Results: Compared with HC, the depression group had an significantly increased variance of dFC in the right superior temporal gyrus (MNI coordinate:33,-12,-12; voxel size 468; t=4.715), extending to the right insula, lentiform nucleus, putamen and Rolandic_Oper_R (aal) (GRF correction, voxel-P<0.005,cluster-P<0.05). Significant negative correlations were observed between the variance in the different brain regions and the total scores andthe factor of retardation scores of HAMD-17 as well the total time, the time of correct thinking, the time of mistake thinking and the number of non-persistent errors of WSCT in depression groups (r=-0.388, -0.365, -0.488, -0.470, -0.412, -0.390, respectively, all P<0.05). Conclusion: The variability of the dFC between the DRN and the temporal insula regions as well as striatum was increased in adolescent patients with untreated depression and associated with the severity and cognitive abnormality.

Performance of a deep neural network in teledermatology: a single-centre prospective diagnostic study.

BACKGROUND: The use of artificial intelligence (AI) algorithms for the diagnosis of skin diseases has shown promise in experimental settings but has not been yet tested in real-life conditions. OBJECTIVE: To assess the diagnostic performance and potential clinical utility of a 174-multiclass AI algorithm in a real-life telemedicine setting. METHODS: Prospective, diagnostic accuracy study including consecutive patients who submitted images for teledermatology evaluation. The treating dermatologist chose a single image to upload to a web application during teleconsultation. A follow-up reader study including nine healthcare providers (3 dermatologists, 3 dermatology residents and 3 general practitioners) was performed. RESULTS: A total of 340 cases from 281 patients met study inclusion criteria. The mean (SD) age of patients was 33.7 (17.5) years; 63% (n = 177) were female. Exposure to the AI algorithm results was considered useful in 11.8% of visits (n = 40) and the teledermatologist correctly modified the real-time diagnosis in 0.6% (n = 2) of cases. The overall top-1 accuracy of the algorithm (41.2%) was lower than that of the dermatologists (60.1%), residents (57.8%) and general practitioners (49.3%) (all comparisons P < 0.05, in the reader study). When the analysis was limited to the diagnoses on which the algorithm had been explicitly trained, the balanced top-1 accuracy of the algorithm (47.6%) was comparable to the dermatologists (49.7%) and residents (47.7%) but superior to the general practitioners (39.7%; P = 0.049). Algorithm performance was associated with patient skin type and image quality. CONCLUSIONS: A 174-disease class AI algorithm appears to be a promising tool in the triage and evaluation of lesions with patient-taken photographs via telemedicine.

Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Transplant outcomes in kidney recipients with lupus nephritis, and systematic review.

BACKGROUND: Despite improved survival of patients with lupus nephritis (LN), some require kidney transplantation because of progression to end-stage renal disease (ESRD). However, the transplant outcomes of these patients and other recipients have not been thoroughly compared. METHODS: In total, 1848 Korean kidney recipients who underwent transplantation from 1998 to 2017 at two tertiary referral centers were evaluated retrospectively. Among them, 28 recipients with LN, and 50 control recipients matched by age, sex, and donor type, were compared with respect to graft and patient survival. We pooled our data with 17 previous cohort studies in which the graft survival of recipients with LN was described in detail. RESULTS: During the median follow-up period of 9.5 years (maximum 21 years), graft failure (GF) occurred in 10.7% and 16.0% of LN and control recipients, respectively. No differences were found in the rates of GF and death-censored graft failure or patient survival between the two groups. The risks of acute T cell-mediated and antibody-mediated rejection were also similar between the two groups. The pooled analysis showed similar 1- and 5-year graft survival rates between LN and control recipients. CONCLUSIONS: Kidney transplantation is an acceptable option in patients with concurrent LN and ESRD.

Outcomes of locking plate fixation with fibular allograft augmentation for proximal humeral fractures in osteoporotic patients: comparison with locking plate fixation alone.

AIMS: The aim of this study was to evaluate the clinical and radiological outcomes of locking plate fixation, with and without an associated fibular strut allograft, for the treatment of displaced proximal humeral fractures in elderly osteoporotic patients. PATIENTS AND METHODS: We undertook a retrospective comparison of two methods of fixation, using a locking plate without an associated fibular strut allograft (LP group) and with a fibular allograft (FA group) for the treatment of these fractures. The outcome was assessed for 52 patients in the LP group and 45 in the FA group, with a mean age of 74.3 years (52 to 89), at a mean follow-up of 14.2 months (12 to 19). The clinical results were evaluated using a visual analogue scale (VAS) score for pain, the Constant score, the American Shoulder and Elbow Surgeons (ASES) score, and the range of movement. Radiological results were evaluated using the neck-shaft angle (NSA) and humeral head height (HHH). RESULTS: The mean forward elevation in the LP and FA groups was 125.3° (sd 21.4) and 148.9° (sd 19.8), respectively (p = 0.042), while other clinical factors showed no statistically significant differences between the groups. The changes in NSA and HHH immediately after the operation and at final follow-up were significantly better in the FA group than in the LP group (p = 0.015 and p = 0.021, respectively). CONCLUSION: For comminuted proximal humeral fractures in osteoporotic patients, locking plate fixation with a fibular strut allograft shows satisfactory short-term results with respect to humeral head support and maintenance of reduction, and may reduce the incidence of complications associated with fixation using a locking plate alone. Cite this article: Bone Joint J 2019;101-B:260-265.

Primary Osteoma Cutis in the Interscapular Region of a Dog.

A 9-year-old neutered male Shih Tzu was presented with three contiguous firm nodules in the subcutaneous tissue of the interscapular region. Histopathological examination revealed that the nodules consisted of mature lamellar bone with a Haversian system, with no apparent lesion around the bone. Clinical examination revealed that the dog had no underlying disease and no history of trauma at the lesion site. Based on these findings and on the medical history, a diagnosis of primary osteoma cutis was made. Osteoma cutis is rare in both human and veterinary medicine, and most dogs reported to have secondary osteoma cutis. To our knowledge, this case is only the second report of primary osteoma cutis in a dog.

[Epidemiological characteristics on temporal-spatial distribution of varicella in Guangxi Zhuang Autonomous Region, 2014-2016].

Objective: To analyze the epidemiological characteristics of temporal-spatial distribution on varicella in Guangxi Zhuang Autonomous Region (Guangxi) during 2014 to 2016. Methods: Incidence data on varicella was collected from the National Notifiable Infectious Disease Reporting Information System (NNIDRIS) of the Center for Disease Control and Prevention (CDC) while geographic information data was from the national CDC. ArcGIS 10.2 software was used to analyze global and local spatial auto correlation on spatial clusters. SaTScan v9.1.1 was used to conduct temporal-spatial scan for exploring the areas of temporal-spatial clusters. Results: The overall incidence rates of varicella during 2014 to 2016 were 32.48/100 000, 43.56/100 000 and 61.56/100 000 respectively. Incidence of varicella showed a positive spatial auto correlation at the county level (the value of Moran's I was between 0.24 to 0.35, P<0.01), with consistent high morbidity. High-high cluster areas were seen and mainly concentrated in the north-western areas of Guangxi. Result from the temporal-spatial scan showed that temporal cluster of varicella occurred mainly between October and next January while the type Ⅰ cluster area was mainly distributed in all of the counties in Hechi city and most counties of Baise city, with most counties being covered in the north-western areas of Guangxi, during 2014-2016. When comparing to data from the last two years, two type Ⅱ cluster areas with larger scales were formed in the north-eastern area of Guanyang county and Haicheng county of southern area in Guangxi, in 2016. Conclusions: Incidence on Varicella seemed on the rise, and the distribution of cases showed clustered features, both on time and space. Strategies regarding control and prevention on Varicella should focus on high-high clustered areas, namely north-western areas of the province, including surrounding areas during the high onset season.

Randomized clinical trial of preoperative skin antisepsis with chlorhexidine gluconate or povidone-iodine.

BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection (SSI); few trials have reported the superiority of any specific agent in clean-contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS: Consecutive patients who underwent clean-contaminated upper gastrointestinal or hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone-iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI. RESULTS: A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone-iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (P = 0·853). The most common causative organism was Enterococcus faecalis. In subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI. CONCLUSION: No difference was detected between chlorhexidine gluconate and povidone-iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (http://www.clinicaltrials.gov).

Transgenic mouse model of IgM+ lymphoproliferative disease mimicking Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a low-grade incurable immunoglobulin M+ (IgM+) lymphoplasmacytic lymphoma for which a genetically engineered mouse model of de novo tumor development is lacking. On the basis of evidence that the pro-inflammatory cytokine, interleukin 6 (IL6), and the survival-enhancing oncoprotein, B cell leukemia 2 (BCL2), have critical roles in the natural history of WM, we hypothesized that the enforced expression of IL6 and BCL2 in mice unable to perform immunoglobulin class switch recombination may result in a lymphoproliferative disease that mimics WM. To evaluate this possibility, we generated compound transgenic BALB/c mice that harbored the human BCL2 and IL6 transgenes, EµSV-BCL2-22 and H2-Ld-hIL6, on the genetic background of activation-induced cytidine deaminase (AID) deficiency. We designated these mice BCL2+IL6+AID- and found that they developed-with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)-a severe IgM+ lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2+IL6+AID- model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM.

Mortality and predictors in pulmonary tuberculosis with respiratory failure requiring mechanical ventilation.

OBJECTIVE: To analyse the predictors and mortality rate among patients receiving mechanical ventilation (MV) for respiratory failure due to pulmonary tuberculosis (TB). DESIGN: We retrospectively compared patients who required MV for TB with patients who required MV for community-acquired pneumonia (CAP). RESULTS: In-hospital mortality was significantly different between the two groups: 95.1% in TB vs. 62.7% in CAP (P < 0.001 using the χ(2) test). TB patients had a higher 30-day mortality (P = 0.040 using log-rank test), although the median sequential organ failure assessment (SOFA) (7.0 vs. 6.0, P = 0.842) and mean Acute Physiology and Chronic Health Evaluation (APACHE) II scores (20.0 ± 6.7 vs. 21.2 ± 6.7, P = 0.379) for TB and CAP patients were not different. TB patients were more likely to have increased lung lesion intrusions (OR 1.307, 95%CI 1.042-1.641, P = 0.021), and reduced albumin (OR 0.073, 95%CI 0.016-0.335, P = 0.001), C-reactive protein (OR 0.324, 95%CI 0.146-0.716, P = 0.005) and CURB-65 score (confusion, uraemia, respiratory rate, blood pressure and age ⩾65 years) (OR 0.916, 95%CI 0.844-0.995, P = 0.037). CONCLUSIONS: TB patients showed identical SOFA and APACHE II scores, but higher mortality than CAP patients. The higher mortality was not related to severity, but suggested an association with the extent of destructive lung lesions.

The anomalous canal between two accessory foramina on the mandibular ramus: the temporal crest canal.

OBJECTIVES: The temporal crest canal (TCC) is a variation of the bony canal with two accessory foramina that correspond to an entrance and an exit on the mandibular ramus. This study investigated the anatomical characteristics of the TCC using CBCT. METHODS: The study population consisted 446 patients who had undergone CBCT. Sagittal, cross-sectional and three-dimensional images were evaluated for the presence of a TCC. The canals were classified into two types according to the configuration, and the location of the posterior accessory foramen of the TCC was also recorded. RESULTS: 6 TCCs were present in 4 of 446 patients (0.90% of the total population). All of the TCCs were observed in males, and all of the posterior foramina were located superior to the mandibular foramina on the medial aspect of the mandibular ramus. There were five noticeably curved and increasingly narrow canals (Type 1) and one slightly curved and uniformly wide canal (Type 2). CONCLUSIONS: Precise knowledge of the TCC is clinically important for suitable local anaesthetic nerve block and the planning of surgical procedures that involve the mandibular ramus. Three-dimensional images of CBCT data are particularly effective for confirming the presence of this variation.

Pulmonary tuberculosis among patients hospitalised with community-acquired pneumonia in a tuberculosis-prevalent area.

SETTING: A suburban teaching hospital in a tuberculosis (TB) prevalent area. OBJECTIVES: To evaluate the proportion of pulmonary TB among patients hospitalised with suspected community-acquired pneumonia (CAP), and to develop a diagnostic index for identifying TB among these patients. DESIGN: TB cases confirmed using 1) sputum culture, or 2) both sputum acid-fast bacilli smear and polymerase chain reaction for Mycobacterium tuberculosis, were compared with non-tuberculous CAP by demographic, clinical, laboratory and radiographic information. Using multiple logistic regression analysis, risk factors for TB were identified. A diagnostic index was developed by summing up their simplified regression coefficients. Its performance was checked using c-statistic. RESULTS: TB was the second leading cause of CAP (37/528, 7.0%). Risk factors were initial symptoms >7 days, serum albumin <3.5 g/dl, cavitary/nodular infiltrates and upper lobe involvement (1 point for each). The c-statistic of the index was 0.856 (95%CI 0.789-0.923), and for bootstrapping samples of 1000 repetitions it was 0.856 (95%CI 0.791-0.921). For scores ≥2, sensitivity and specificity were respectively 81.1% and 75.8%. CONCLUSION: TB is one of the leading causes of CAP in TB-prevalent areas. Our diagnostic index may help clinicians identify TB immediately from CAP and initiate appropriate isolation and optimal treatment.

Identification of the effects of aging-related gene-matrix metalloproteinase on allograft outcomes in kidney transplantation.

BACKGROUND: Aging plays a profound role in the ability of the kidney to function. Aging which varies among individuals, has been associated with the matrix metalloproteinase (MMP) 7 and 20 genes. This study was conducted to analyze correlations between polymorphisms of MMP genes [rs880197 in MMP7 (A>T) and rs1711437 in MMP20 (G>A)] and transplant outcomes in 235 recipients. METHODS: Transplant outcomes were evaluated according to the sum of the A alleles in the recipients and the donors. The group with a high number of A alleles (≥3) was compared with the group with a low number (<3). RESULTS: The group with a high number of MMP7 A alleles showed a lower risk of chronic tubulointerstitial lesion than the group with a low number (P = .009). The group with a high number of MMP20 A alleles had showed better long-term kidney function at 10 years after transplantation than the group with a low number (P = .026). Furthermore, the group with a high number of MMP20 A alleles showed a trend toward better graft survival compared with the group with a low number, especially among recipients followed for >1 year (P = .022). CONCLUSIONS: Polymorphisms of MMP7 and MMP20 genes may be surrogate markers to predict long-term outcomes after kidney transplantation.

Scaling of the low-energy structure in above-threshold ionization in the tunneling regime: theory and experiment.

A calculation of the second-order (rescattering) term in the S-matrix expansion of above-threshold ionization is presented for the case when the binding potential is the unscreened Coulomb potential. Technical problems related to the divergence of the Coulomb scattering amplitude are avoided in the theory by considering the depletion of the atomic ground state due to the applied laser field, which is well defined and does not require the introduction of a screening constant. We focus on the low-energy structure, which was observed in recent experiments with a midinfrared wavelength laser field. Both the spectra and, in particular, the observed scaling versus the Keldysh parameter and the ponderomotive energy are reproduced. The theory provides evidence that the origin of the structure lies in the long-range Coulomb interaction.

Common genetic variants in the 9p21 region and their associations with multiple tumours.

BACKGROUND: The chromosome 9p21.3 region has been implicated in the pathogenesis of multiple cancers. METHODS: We systematically examined up to 203 tagging SNPs of 22 genes on 9p21.3 (19.9-32.8 Mb) in eight case-control studies: thyroid cancer, endometrial cancer (EC), renal cell carcinoma, colorectal cancer (CRC), colorectal adenoma (CA), oesophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma and osteosarcoma (OS). We used logistic regression to perform single SNP analyses for each study separately, adjusting for study-specific covariates. We combined SNP results across studies by fixed-effect meta-analyses and a newly developed subset-based statistical approach (ASSET). Gene-based P-values were obtained by the minP method using the Adaptive Rank Truncated Product program. We adjusted for multiple comparisons by Bonferroni correction. RESULTS: Rs3731239 in cyclin-dependent kinase inhibitors 2A (CDKN2A) was significantly associated with ESCC (P=7 × 10(-6)). The CDKN2A-ESCC association was further supported by gene-based analyses (Pgene=0.0001). In the meta-analyses by ASSET, four SNPs (rs3731239 in CDKN2A, rs615552 and rs573687 in CDKN2B and rs564398 in CDKN2BAS) showed significant associations with ESCC and EC (P<2.46 × 10(-4)). One SNP in MTAP (methylthioadenosine phosphorylase) (rs7023329) that was previously associated with melanoma and nevi in multiple genome-wide association studies was associated with CRC, CA and OS by ASSET (P=0.007). CONCLUSION: Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.

Ultrasonographic investigation of the effect of positive end-expiratory pressure on the cross-sectional area of the femoral vein.

Femoral veins are commonly used as a relatively safe alternative route for central venous cannulation. Several maneuvers are used to increase the cross-sectional area of the vein. In this study, we assessed the effect of positive end-expiratory pressure (PEEP) on the cross-sectional area (CSA) of femoral veins, using ultrasound in adult patients under positive pressure ventilation. All patients received a standardized induction of general anesthesia and intravenous fluid administration. Using ultrasound, the cross-sectional areas of both femoral veins were measured in 57 adult patients in the supine position without PEEP (control) and in the supine position with PEEP of 10 cm H(2)O. Mean arterial pressure and heart rate were recorded before and after the application of PEEP at 10 cm H(2)O. The application of 10 cm H(2)O PEEP significantly increased the CSA of the right femoral vein by 47.6 % and the left femoral vein by 48.4 % (each P < 0.001). Mean arterial pressure decreased by 2.6 mmHg (95 % CI 1.3-3.9; P < 0.001), whereas no significant change in heart rate was observed (P = 0.861). The CSA of the femoral vein is augmented with the application of 10 cm H(2)O PEEP in adult patients undergoing positive pressure ventilation.

Relationship between positive end-expiratory pressure and internal jugular vein cross-sectional area.

BACKGROUND: Application of positive end-expiratory pressure (PEEP) has been used to increase the cross-sectional area (CSA) of the right internal jugular vein (IJV) in order to facilitate catheterisation. We aimed to determine the PEEP level at which the maximum increase of CSA occurred. METHODS: We enrolled 60 American Society of Anesthesiologists physical status I and II patients undergoing general endotracheal anaesthesia. The CSA was measured in the supine position with no PEEP (control condition, P0) and after applying five different PEEPs in random order: 3 (P3), 6 (P6), 9 (P9), 12 (P12), and 15 (P15) cm H(2) O. Ultrasound was used to measure and record the CSA of the right IJV at the level of the cricoid cartilage. RESULTS: All PEEP levels increased the CSA of the right IJV relative to the control (all P < 0.05). On average, P3, P6, P9, P12, and P15 increased the CSA by 21.5, 37.4, 51.9, 66.5, and 72.4%, respectively. There was no significant increase in CSA above a PEEP of 12 cm H(2) O. CONCLUSION: The application of PEEP effectively increases the CSA of the right IJV. The PEEP giving the largest CSA is 12 cm H(2) O.

T-category reflects the histopathologic characteristics of gallbladder cancer.

AIMS: Gallbladder (GB) cancer is a relatively uncommon gastrointestinal malignancy and is known to often result in unfavorable outcomes. Recent advances in aggressive surgical resection have improved the overall survival rate of patients with GB cancer. We aimed to evaluate the outcomes and prognostic factors of GB cancer following a surgical resection with curative intent. METHODS: Between March 2001 and March 2009, 89 patients with GB cancer underwent surgical resection with curative intent at the National Cancer Center of Korea. We then conducted a retrospective analysis of clinicopathologic data. RESULTS: Nineteen patients underwent simple cholecystectomy and 70 patients underwent extended cholecystectomy. Tumor-free resection margins were obtained in 84 cases. The 1-, 3- and 5-year disease-specific survival rates in the 89 patients were 85.8%, 68.0% and 64.1%, respectively. By multivariate analysis, only the T-category was significant (p < 0.001). The T-category showed a close correlation with all of the other histopathologic factors which were significant in univariate analysis. CONCLUSION: The T-category of GB cancer represents not only the depth of the primary tumor but also the aggressiveness of its histopathologic nature.