Valoración de parámetros clínicos y analíticos preoperatorios en apendicitis aguda complicada. Score para predecir apendicitis complicada

BackgroundTo analyze whether clinical and analytical parameters differ according to histopathology in cases of acute appendicitis (AA).MethodsThis is a retrospective, observational study including patients (>14 years of age) admitted for suspicion of AA from 1 April 2014 to 31 July 2016. Histopathology was divided into complicated (including perforated and gangrenous AA) and uncomplicated appendicitis (phlegmonous). Sex, age, temperature of patients on admission to the Emergency Department, symptom duration, preoperative white blood cell (WBC) count, neutrophil percentage, mean platelet volume (MPV), platelet distribution width (PDW), C-reactive protein (CRP) and hospital stay were compared in the two groups.ResultsThree hundred and thirty-five patients were analyzed, and 284 were included. Appendicitis was uncomplicated in 194 (68.3%) and complicated in 90 (31.7%). Age, symptom duration, neutrophil percentage, CRP and hospital stay were higher in the complicated AA group (P < .05). The mean differences between uncomplicated and complicated AA were: age 13.2 years (95% CI: 8.2-18.2), symptom duration 14.1 hours (95% CI: 6.3-21.9), neutrophil percentage 5.0% (95% CI: 3.2-6.8), CRP 73.6 mg/l (95% CI: 50.0-97.2) and hospital stay 2.2 days (95% CI: 1.4-3.0), with p<0.05 for all these variables. A model based on the preoperative parameters (age, symptom duration, neutrophil percentage and CRP) was calculated to predict the likelihood of complicated AA. The receiver operating characteristic (ROC) of the model had an area under the curve of 0.80 (95% CI 0.75-0.85).ConclusionThis model is able to diagnose complicated AA without the need for imaging techniques, although it must be validated with prospective analysis.     

miR-320c Regulates SERPINA1 Expression and Is Induced in Patients With Pulmonary Disease

IntroductionAlpha-1 antitrypsin deficiency (AATD) is a genetic condition resulting in lung and liver disease with a great clinical variability. MicroRNAs have been identified as disease modifiers; therefore miRNA deregulation could play an important role in disease heterogeneity. Members of miR-320 family are involved in regulating of multiple processes including inflammation, and have potential specific binding sites in the 3′UTR region of SERPINA1 gene. In this study we explore the involvement of miR-320c, a member of this family, in this disease.MethodsFirstly in vitro studies were carried out to demonstrate regulation of SERPINA1 gene by miR-320. Furthermore, the expression of miR-320c was analyzed in the blood of 98 individuals with different AAT serum levels by using quantitative PCR and expression was correlated to clinical parameters of the patients. Finally, HL60 cells were used to analyze induction of miR-320c in inflammatory conditions.ResultsOverexpression of miR-320 members in human HepG2 cells led to inhibition of SERPINA1 expression. Analysis of miR-320c expression in patient's samples revealed significantly increased expression of miR-320c in individuals with pulmonary disease. Additionally, HL60 cells treated with the pro-inflammatory factor lipopolysaccharide (LPS) showed increase in miR-320c expression, suggesting that miR-320c responds to inflammation.ConclusionOur findings demonstrate that miR-320c inhibits SERPINA1 expression in a hepatic cell line and its levels in blood are associated with lung disease in a cohort of patients with different AAT serum levels. These results suggest that miR-320c can play a role in AAT regulation and could be a biomarker of inflammatory processes in pulmonary diseases.     

Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.     

Locomotive Syndrome is associated with chronic pain and poor quality of life in Brazilian oldest old: LOCOMOV Project

BackgroundIn 2007, the Japanese Orthopedic Association established the term “Locomotive Syndrome” (LS) for the concept of locomotor organ dysfunction with potential loss of independence. The purpose of this study was to identify characteristics of LS and establish a diagnostic cut-off for the Geriatric Locomotive Function Scale (GLFS 25-p) for the Brazilian population.MethodsA cross-sectional observational study of the LOCOMOV Project cohort of independent outpatients aged ≥80 years was conducted. Questionnaires on functional status in Basic and Instrumental Activities of Daily Living (Katz and Lawton, respectively) and quality of life (WHOQOL-Bref) were applied, together with the Geriatric Locomotive Function Scale (GLFS 25-p) to identify individuals with LS. Mobility was assessed using the five-times sit-to-stand test, 4-m gait speed, two-step test, one-leg standing time with eyes open and hand-grip test. The data were analyzed using Student's t-test, the Chi–Square test, and multiple logistic regression (stepwise). The significance level was set at 0.05 (5%).ResultsA sample of 102 individuals with mean age of 87.3 (±4.2) years and predominantly female (73.5%) was assessed. We determined a cut-off score of 19 (sensitivity of 0.86 and specificity of 0.67) for diagnosis of LS, as assessed by the GLFS 25-p, and a high prevalence (55%) of the syndrome was found in the sample. In the multiple regression analysis, LS was directly associated with chronic pain (OR 22.24, 95%CI 3.13–157.87), use of a walking device (OR 17.121, 95%CI 1.94–150.49), and inversely associated with gait speed ≥0.8 m/s (OR 0.42, 95%CI 0.006–0.278), perception of good health (OR 0.153, 95%CI 0.029–0.799) and male gender (OR 0.086, 95%CI 0.0105–0.714).ConclusionThe LS in the oldest old proved a very common condition in this survey, especially in women, and was strongly associated with chronic pain, worse performance on physical tests and poor quality of life.     

Compound heterozygous mutations in the SRD5A2 gene exon 4 in a male pseudohermaphrodite patient of Chinese origin

The goal of this study was to perform 5-alpha-reductase type 2 gene (SRD5A2) analysis in a male pseudohermaphrodite (MPH) patient with normal testosterone (T) production and normal androgen receptor (AR) gene coding sequences. A patient of Chinese origin with ambiguous genitalia at 14 months, a 46,XY karyotype, and normal T secretion under human chorionic gonadotropin (hCG) stimulation underwent a gonadectomy at 20 months. Exons 1-8 of the AR gene and exons 1-5 of the SRD5A2 gene were sequenced from peripheral blood DNA. AR gene coding sequences were normal. SRD5A2 gene analysis revealed 2 consecutive mutations in exon 4, each located in a different allele: 1) a T nucleotide deletion, which predicts a frameshift mutation from codon 219, and 2) a missense mutation at codon 227, where the substitution of guanine (CGA) by adenine (CAA) predicts a glutamine replacement of arginine (R227Q). Testes located in the inguinal canal showed a normal morphology for age. The patient was a compound heterozygote for SRD5A2 mutations, carrying 2 mutations in exon 4. The patient showed an R227Q mutation that has been described in an Asian population and MPH patients, along with a novel frameshift mutation, Tdel219. Testis morphology showed that, during early infancy, the 5-alpha-reductase enzyme deficiency may not have affected interstitial or tubular development.     

Peritoneal dialysis with solutions low in glucose degradation products is associated with improved biocompatibility profile towards peritoneal mesothelial cells.

BACKGROUND: In vitro experiments point to a better biocompatibility profile of new pH-neutral peritoneal dialysis fluids (PDFs) containing low levels of glucose degradation products (GDPs). The present study examines the impact on human peritoneal mesothelial cells (HPMCs) of equilibrated dialysates obtained during dialysis with either conventional or new PDFs. METHODS: Peritoneal dialysate was collected from 17 patients participating in a randomized, controlled, cross-over trial comparing a pH-neutral low-GDP solution (Balance) to a conventional solution (S-PDF). All patients were treated sequentially for 3 months with both PDFs. At the end of each treatment phase, peritoneal effluent was drained after a timed 10 h dwell. Samples of dialysate were then mixed with standard culture medium and added to in vitro cultures of HPMCs from healthy donors. Cells were assessed for proliferation, viability and cytokine release. RESULTS: Proliferation and viability of HPMCs were better preserved in the presence of effluent obtained during dialysis with Balance (P<0.046 and P<0.035, respectively). The proliferative response of HPMCs correlated with the concentration of fibronectin in dialysates (P = 0.0024). Effluent drained following a 3 month dialysis with Balance contained significantly increased levels of fibronectin (P = 0.004) and CA125 antigen (P = 0.0004) compared with S-PDF. There was no significant difference in constitutive and stimulated cytokine (IL-6, MCP-1, VEGF) synthesis by HPMCs treated with either Balance- or S-PDF-derived effluents. CONCLUSIONS: These results suggest that therapy with new pH-neutral low-GDP solutions contribute to an intraperitoneal milieu that improves mesothelial cell proliferation and viability. It may positively impact on the preservation of the peritoneal membrane integrity during long-term dialysis.     

Neuroendocrine and biologic features of primary tumors and tissue in pulmonary large cell carcinomas

BACKGROUND: Because biological behavior in lung tumors with neuroendocrine differentiation is highly dependent on cell death (apoptosis) and angiogenesis, p21(waf1/cip1) and microvessel density have been targeted as potentially useful tumor markers. We sought to validate the importance of p21(waf1/cip1) and microvessel density and study their interrelationship, analyzing clinical factors, subclassifications, and tumor and stromal markers. METHODS: We examined p21(waf1/cip1) and other markers in tissue from 61 patients with surgically excised large cell carcinomas. The amount of tumor staining for p21(waf1/cip1) and microvessel density was evaluated by immunohistochemistry and morphometry. The study outcome was survival time until death from recurrent lung cancer. RESULTS: Multivariate Cox model analysis demonstrated that after surgical excision, histologic subtypes were significantly related to survival time (p = 0.02), but quantitative staining of the tumor for p21(waf1/cip1) and microvessel density added prognostic information and these variables were more strongly prognostic than histologic subtype (p = 0.00). Cut points at the median staining of 3.5% and 3.0% for p21(waf1/cip1) and microvessel density, respectively, divided patients into two groups with distinctive survival times. Patients with p21(waf1/cip1) staining of more than 3.5% and microvessel density staining of more than 3.0% had a median survival time of 14 months. CONCLUSIONS: Tumor staining for p21(waf1/cip1) and microvessel density in resected large cell carcinomas and certain other types of lung tumors was strongly related to survival. Patients with more than 3.0% staining in their tumors were at high risk of death from lung cancer and may be an appropriate target for prospective studies of adjuvant chemotherapy after surgical resection.     

11C-methionine PET/CT in 99mTc-sestamibi-negative hyperparathyroidism in patients with renal failure on chronic haemodialysis

Purpose Scintigraphic localisation of parathyroid glands is often unsuccessful in patients with renal failure on chronic haemodialysis who have secondary hyperparathyroidism (HPT). The purpose of this study was to investigate the use of ¹¹C-methionine PET/CT to detect hyperfunctioning parathyroid glands in patients with renal failure on chronic haemodialysis who had ^99mTc-sestamibi-negative HPT. Methods ¹¹C-methionine PET/CT was performed in 18 patients (11 women and 7 men, aged 42–79 years; mean age 57.8 years) on haemodialysis for renal failure (2–14 years’ duration), with normo-, hypo- or hypercalcaemia and HPT not localised by either dual-tracer ^99mTc-pertechnetate/^99mTc-sestamibi subtraction scans or dual-phase ^99mTc-sestamibi scans. Results In three of ten patients with normo- or hypocalcaemic HPT there was increased ¹¹C-methionine accumulation in one gland. Seven of eight patients with hypercalcaemic HPT showed increased uptake: in five of these patients increased ¹¹C-methionine accumulation was present in one gland, while in two it was demonstrated in two glands. All patients also had high-resolution ultrasound of the neck and were treated with subtotal parathyroidectomy, leaving a remnant of the smallest of the four glands. Regardless of their size, all glands with abnormal ¹¹C-methionine parathyroid uptake were removed, and all demonstrated parathyroid hyperplasia. All patients developed post-parathyroidectomy hypoparathyroidism and one patient with normocalcaemic HPT relapsed 8 months after surgery. Conclusion These data suggest that ¹¹C-methionine PET/CT may be used to identify hyperfunctioning parathyroid glands in non-primary HPT, and especially hypercalcaemic HPT, when conventional ^99mTc-sestamibi imaging is non-localising.     

Lymph node metastasis in patients with clinical early-stage cervical cancer: detection with integrated FDG PET/CT

PURPOSE: To prospectively determine the accuracy of combination positron emission tomography-computed tomography (PET/CT) in lymph node staging in patients with early-stage cervical cancer, with histopathologic results as the reference standard. MATERIALS AND METHODS: The study was institutional review board approved, and all patients gave informed consent. Forty-seven consecutive women aged 29-71 years with clinical stage IA or IB cervical carcinoma were included in the study. All 47 patients were scheduled for radical hysterectomy with pelvic lymph node dissection. Before surgery, all patients underwent fluorine 18 fluorodeoxyglucose (FDG) PET/CT. PET/CT findings were interpreted by two readers in consensus and then compared with histopathologic results. At histopathologic examination, the dissected lymph nodes were classified as nonmetastatic or metastatic. RESULTS: Fifteen (32%) patients had metastatic lymph nodes at histopathologic examination, and 32 (68%) had no histopathologically confirmed nodal metastasis. Of the total 1081 lymph nodes histopathologically sampled, 18 were found to be positive for malignant cells. The overall node-based sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT were 72% (13 of 18), 99.7% (1060 of 1063), 81% (13 of 16), 99.5% (1060 of 1065), and 99.3% (1073 of 1081), respectively. Corresponding values for PET/CT-based diagnosis of lymph nodes larger than 0.5 cm in diameter were 100% (13 of 13), 99.6% (675 of 678), 81% (13 of 16), 100% (675 of 675), and 99.6% (688 of 691), respectively. The overall patient-based sensitivity, specificity, PPV, NPV, and accuracy of PET/CT were 73% (11 of 15), 97% (31 of 32), 92% (11 of 12), 89% (31 of 35), and 89% (42 of 47), respectively. CONCLUSION: PET/CT proved to be valuable for lymph node staging in patients with early-stage cervical cancer, with short-axis diameter greater than 0.5 cm being the size threshold for accurate depiction of metastatic nodes.