Neurotoxicity and safety of the rechallenge of immune checkpoint inhibitors: a growing issue in neuro-oncology practice.

Neurological, immune-related adverse events (n-irAE) due to immune checkpoint inhibitors (ICI) represent a growing clinical problem in neuro-oncology practice. Although rare, the frequency of n-irAEs will increase as ICI use becomes more common. Central and peripheral nervous systems may be involved, and multiple n-irAEs like myositis, myasthenia gravis, and myocarditis can arise in the same patient. Prompt recognition, initial ICI discontinuation, and treatment with immunosuppressive therapy comprise key aspects of managing these potentially fatal neurological complications. Severe and/or treatment-refractory n-irAEs may occur and require individualized care. In the same vein, a possible reintroduction of ICI after a n-irAE represents an additional challenge in clinical practice. An approach by experienced neurologists involved in highly subspecialized, multidisciplinary care teams is, therefore, of major importance in managing these cases. The present study updates current knowledge regarding presentation forms, diagnostic workflows, outcomes, and general management of n-irAEs. With the aim to guide neurologists in decision-making processes during such scenarios, the study further reviews available data on ICI reintroduction safety in patients with prior n-irAEs.

The presence of IFL3/4 rs12979860 C allele influences the in vitro IP-10 production by mononuclear cells from patients with systemic lupus erythematosus.

OBJECTIVE: To explore whether the IFNL3/4 rs12979860 genotype may influence serum levels or production of interferon-inducible protein-10 (IP-10) by peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE). METHODS: Sixty-six patients with SLE and 22 healthy blood donors (controls) were included. The IFNL3/4 rs12979860 polymorphism was genotyped by real-time polymerase chain reaction. IP-10 levels in sera supernatants of IFNα stimulated peripheral blood mononuclear cells were measured by enzime-linked immunosorbent assay. RESULTS: Allelic frequencies were CC (29%), CT (52%) and TT (20%) in SLE, and CC (32%), CT (41%) and TT (27%) in healthy controls. Median serum IP-10 levels were higher in SLE patients than in controls (190.8 versus 118.1 pg/ml; p < 0.001), particularly in those with high disease activity (278.5 versus 177.2 pg/ml; p = 0.037). However, serum IP-10 levels were not influenced by IFNL3/4 genotypes. Higher IP-10 production by peripheral blood mononuclear cells was found in both SLE patients (median 519.3 versus 207.6 pg/ml; p = 0.012) and controls (median 454.0 versus 201.7 pg/ml; p = 0.034) carrying the IFNL3/4 C allele compared with carriers of the T allele. CONCLUSIONS: Although IFNL3/4 rs12979860 allele C does not appear to influence serum IP-10 levels in SLE, it plays an important role in the production of IP-10 by peripheral blood mononuclear cells after IFNα stimulation.

Diagnostic delay and outcome in immunocompetent patients with primary central nervous system lymphoma in Spain: a multicentric study.

INTRODUCTION: To assess the management of immunocompetent patients with primary central nervous system lymphomas (PCNSL) in Spain. METHODS: Retrospective analysis of 327 immunocompetent patients with histologically confirmed PCNSL diagnosed between 2005 and 2014 in 27 Spanish hospitals. RESULTS: Median age was 64 years (range: 19-84; 33% ≥ 70 years), 54% were men, and 59% had a performance status (PS) ≥ 2 at diagnosis. Median delay to diagnosis was 47 days (IQR 24-81). Diagnostic delay > 47 days was associated with PS ≥ 2 (OR 1.99; 95% CI 1.13-3.50; p = 0.016) and treatment with corticosteroids (OR 2.47; 95% CI 1.14-5.40; p = 0.023), and it did not improve over the years. Patients treated with corticosteroids (62%) had a higher risk of additional biopsies (11.7% vs 4.0%, p = 0.04) but corticosteroids withdrawal before surgery did not reduce this risk and increased the diagnostic delay (64 vs 40 days, p = 0.04). Median overall survival (OS) was 8.9 months [95% CI 5.9-11.7] for the whole series, including 52 (16%) patients that were not treated, and 14.1 months (95%CI 7.7-20.5) for the 240 (73.4%) patients that received high-dose methotrexate (HD-MTX)-based chemotherapy. Median OS was shorter in patients ≥ 70 years (4.1 vs. 13.4 months; p < 0.0001). Multivariate analysis identified age ≥ 65 years, PS ≥ 2, no treatment, and cognitive/psychiatric symptoms at diagnosis as independent predictors of short survival. CONCLUSIONS: Corticosteroids withdrawal before surgery does not decrease the risk of a negative biopsy but delays diagnosis. In this community-based study, only 73.4% of patients could receive HD-MTX-based chemotherapy and OS remains poor, particularly in elderly patients ≥ 70 years.

Levels of anti-Müllerian hormone in premenopausal women with the antiphospholipid syndrome and its association with the risk of clinical complications.

OBJECTIVE: The study aims to investigate the ovarian reserve in premenopausal women with antiphospholipid syndrome (APS) and to evaluate whether it is associated with cumulative organ damage or the risk of clinical complications. METHODS: This single-center study was conducted in 23 premenopausal female patients (10 with primary APS and 13 with secondary APS) and 24 healthy volunteers. Serum anti-Müllerian hormone (AMH) levels were measured by enzyme-linked immunoassay. Disease-specific organ damage (DIAPS score) and the risk of clinical complications (aGAPSS score) were additionally evaluated in APS patients. RESULTS: Serum AMH levels were similar in APS patients (median 6.06, interquartile range 4.31-7.54 ng/ml) and in controls (4.87, 2.64-6.40 ng/ml; P = 0.116), and no differences were observed between the primary (6.60, 5.49-8.88 ng/ml) and secondary (6.06, 3.91-7.30 ng/ml; P = 0.532) forms of the syndrome. In individuals with APS, serum AMH levels correlated inversely with the aGAPSS score (rho-0.421, 95% confidence intervals -0.716 to -0.001; P = 0.045), while no associations were observed with the DIAPS score (rho-0.001, -0.423 to 0.422; P = 0.996). CONCLUSIONS: Ovarian reserve is not reduced in premenopausal women with APS. In addition, serum AMH levels may reflect the risk of APS-related clinical complications but not the burden of disease-specific organ damage.

An imbalance in the T-helper phenotypes displayed by senescent CD4+CD28null T cells is associated with erosive arthritis (rhupus syndrome) in systemic lupus erythematosus.

OBJECTIVE: The objective was to assess the proportion of Th1, Th2 and Th17 phenotypes in senescent CD4+CD28null cells from patients with systemic lupus erythematosus (SLE) and its association with the pattern of joint involvement. METHODS: This cross-sectional study was performed in SLE patients with erosive arthritis (rhupus) or nondeforming, nonerosive arthritis. Total CD4+CD28null cells as well as the proportion of these cells expressing T-bet, GATA3 or RORγt were analyzed by color-flow cytometry. Serum osteopontin levels were measured by ELISA. RESULTS: Eighteen SLE patients (nine with rhupus and nine with nonerosive arthritis) were studied. The percentage of CD4+CD28null/CD4+ cells (17.7%, 10.3-25.0% versus 9.4%, 8.1-22.4%; P = 0.386) as well as the osteopontin levels (5800, 5,134-5995 pg/ml versus 5578, 5171-5717 pg/ml; P > 0.05) were similar in both groups. A higher percentage of CD4+CD28nullT-bet+ cells (42.8%, 33.5-53.4% versus 30.0%, 23.3-34.2%) but a lower percentage of CD4+CD28nullGATA3+ cells (3.1%, 1.7-5.6% versus 6.2%, 2.6-18.4%) was observed in patients with rhupus than in their counterparts ( P = 0.016). The frequency of CD4+CD28nullRORγt+ cells was similar between groups. CONCLUSIONS: In patients with rhupus, senescent CD4+CD28null cells are preferentially polarized to a Th1 phenotype, whereas this is partial towards Th2 in lupus patients with a nonerosive arthritis pattern.

Validation of a predictive model for identifying febrile young infants with altered urinalysis at low risk of invasive bacterial infection.

In 2015, a predictive model for invasive bacterial infection (IBI) in febrile young infants with altered urine dipstick was published. The aim of this study was to externally validate a previously published set of low risk criteria for invasive bacterial infection in febrile young infants with altered urine dipstick. Retrospective multicenter study including nine Spanish hospitals. Febrile infants ≤90 days old with altered urinalysis (presence of leukocyturia and/or nitrituria) were included. According to our predictive model, an infant is classified as low-risk for IBI when meeting all the following: appearing well at arrival to the emergency department, being >21 days old, having a procalcitonin value <0.5 ng/mL and a C-reactive protein value <20 mg/L. IBI was considered as secondary to urinary tract infection if the same pathogen was isolated in the urine culture and in the blood or cerebrospinal fluid culture. A total of 391 patients with altered urine dipstick were included. Thirty (7.7 %) of them developed an IBI, with 26 (86.7 %) of them secondary to UTI. Prevalence of IBI was 2/104 (1.9 %; CI 95% 0.5-6.7) among low-risk patients vs 28/287 (9.7 %; CI 95% 6.8-13.7) among high-risk patients (p < 0.05). Sensitivity of the model was 93.3 % (CI 95% 78.7-98.2) and negative predictive value was 98.1 % (93.3-99.4). Although our predictive model was shown to be less accurate in the validation cohort, it still showed a good discriminatory ability to detect IBI. Larger prospective external validation studies, taking into account fever duration as well as the role of ED observation, should be undertaken before its implementation into clinical practice.

Reliability and accuracy of quantitative sensory testing for oxaliplatin-induced neurotoxicity.

OBJECTIVES: Thermal quantitative sensory testing (QST) is a non-invasive procedure helpful in the assessment of the function of small Aδ and C nerve sensory fibres. Oxaliplatin (OXA) is an effective chemotherapeutic agent, but is frequently associated with neurotoxic dose-limiting side effects. This controlled clinical trial evaluated the reliability and accuracy of thermal QST for assessing the OXA-induced acute neuropathic syndrome, whose clinical hallmark is cold-triggered painful paraesthesia. MATERIALS & METHODS: A testing protocol with the Thermal Sensory Analyzer (Medoc) was carried out in 20 colorectal cancer patients during the initial four cycles of OXA-based chemotherapy and in 20 age- and sex-matched healthy volunteers. Testing was carried out on the hands and included the determination of thermal detection and pain thresholds and the intensity of pain evoked by cold stimuli. Calculations were made of: coefficients of test-retest and inter-rater reliability, indices of responsiveness and parameters that quantify diagnostic accuracy. RESULTS: Thermal thresholds showed moderate to good reliability (ρ ≥ 0.383), but were not consistently responsive to the effects of chemotherapy (cold pain thresholds decreased in both groups, although almost twice in patients compared to healthy volunteers). Conversely, the intensity of pain evoked by suprathreshold cold stimuli was reliable (ρ ≥ 0.822), responsive (detected changes over time) and discriminated between patients and healthy volunteers (area under the ROC curve = 0.700). CONCLUSIONS: The procedure was reliable and accurate to evaluate cold hyperalgesia resulting from OXA administration. The data provided may be used to define efficacy endpoints for future clinical trials of therapies for OXA-induced neuropathies and calculate appropriate sample sizes.

Physician-assessed and patient-reported outcome measures in chemotherapy-induced sensory peripheral neurotoxicity: two sides of the same coin.

BACKGROUND: The different perception and assessment of chemotherapy-induced peripheral neurotoxicity (CIPN) between healthcare providers and patients has not yet been fully addressed, although these two approaches might eventually lead to inconsistent, possibly conflicting interpretation, especially regarding sensory impairment. PATIENTS AND METHODS: A cohort of 281 subjects with stable CIPN was evaluated with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC v. 2.0) sensory scale, the clinical Total Neuropathy Score (TNSc©), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sumscore (mISS) and the European Organization for Research and Treatment of Cancer CIPN specific self-report questionnaire (EORTC QOL-CIPN20). RESULTS: Patients' probability estimates showed that the EORTC QLQ-CIPN20 sensory score was overall more highly related to the NCI-CTC sensory score. However, the vibration perception item of the TNSc had a higher probability to be scored 0 for EORTC QLQ-CIPN20 scores lower than 35, as vibration score 2 for EORTC QLQ-CIPN20 scores between 35 and 50 and as grade 3 or 4 for EORTC QLQ-CIPN20 scores higher than 50. The linear models showed a significant trend between each mISS item and increasing EORTC QLQ-CIPN20 sensory scores. CONCLUSION: None of the clinical items had a perfect relationship with patients' perception, and most of the discrepancies stood in the intermediate levels of CIPN severity. Our data indicate that to achieve a comprehensive knowledge of CIPN including a reliable assessment of both the severity and the quality of CIPN-related sensory impairment, clinical and PRO measures should be always combined.

[Massive pneumoperitoneum in a newborn with mechanical ventilation in apparent absence of barotrauma]. / Neumoperitoneo masivo en un recién nacido con ventilación mecánica, en ausencia aparente de barotrauma.

Pneumoperitoneum is usually secondary to perforation of gastrointestinal tract. Sometimes it is a barotrauma, especially in newborn infants undergoing mechanical ventilation, causing lung rupture and passage of air from airway into the peritoneum through the mediastinum. It seems less likely that the pneumoperitoneum occurs in a patient undergoing mechanical ventilation, in the absence of a demonstrable barotrauma and a bowel perforation. We present a preterm patient who, on her third day of life, while being subjected to mechanical ventilation, reports a massive pneumoperitoneum with the apparent absence of barotrauma. After the drainage of the peritoneal cavity, the pneumoperitoneum disappears in two days, without laparotomy. The subsequent evolution is favourable.

The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting complication of cancer treatment. Thus far, the impact of CIPN has not been studied in a systematic clinimetric manner. The objective of the study was to select outcome measures for CIPN evaluation and to establish their validity and reproducibility in a cross-sectional multicenter study. PATIENTS AND METHODS: After literature review and a consensus meeting among experts, face/content validity were obtained for the following selected scales: the National Cancer Institute-Common Toxicity Criteria (NCI-CTC), the Total Neuropathy Score clinical version (TNSc), the modified Inflammatory Neuropathy Cause and Treatment (INCAT) group sensory sumscore (mISS), the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and CIPN20 quality-of-life measures. A total of 281 patients with stable CIPN were examined. Validity (correlation) and reliability studies were carried out. RESULTS: Good inter-/intra-observer scores were obtained for the TNSc, mISS, and NCI-CTC sensory/motor subscales. Test-retest values were also good for the EORTC QLQ-C30 and CIPN20. Acceptable validity scores were obtained through the correlation among the measures. CONCLUSION: Good validity and reliability scores were demonstrated for the set of selected impairment and quality-of-life outcome measures in CIPN. Future studies are planned to investigate the responsiveness aspects of these measures.

Advanced age and liability to oxaliplatin-induced peripheral neuropathy: post hoc analysis of a prospective study.

BACKGROUND AND PURPOSE: The aim of this post hoc analysis of data extracted from a prospective, multicenter study is to test in a large homogenous population of chemotherapy-naïve patients with colorectal cancer (CRC) treated with oxaliplatin (OXA)-based chemotherapy whether advanced age increases the risk of developing OXA-induced peripheral neuropathy (OXAIPN). METHODS: One-hundred and forty-five patients with CRC, without other significant co-morbidities predisposing to peripheral neuropathy, were divided according to their age into two groups: patients aged between 50 and 68 years (group I, n = 75); and patients aged ≥ 69 years (group II, n = 70). Patients were prospectively monitored at baseline and followed-up during chemotherapy using the motor and neurosensory National Cancer Institute Common Toxicity criteria, the clinical version of the Total Neuropathy Score and neurophysiology. The incidence and severity of both the acute and cumulative OXAIPN was thoroughly determined and then compared between age groups. RESULTS: No statistically significant difference was observed in the incidence of both the acute (n = 64/75 vs. 56/70; P = 0.510) and cumulative OXAIPN (n = 51/75 vs. 49/70; P = 0.858) between age groups. The severity of OXAIPN was also similar between age groups. In line with the clinical data, the neurophysiological results between age groups were also comparable. CONCLUSION: The results of this study indicate that advanced age does not seem to represent a significant risk factor of OXAIPN in patients with CRC without any other significant co-morbidities.

Imaging of Lymphomas Involving the CNS: An Update-Review of the Full Spectrum of Disease with an Emphasis on the World Health Organization Classifications of CNS Tumors 2021 and Hematolymphoid Tumors 2022.

Lymphomas of the CNS are the second most frequent primary brain malignancy in adults after gliomas. Presurgical suspicion of lymphoma greatly impacts patient management. The radiologic features of this tumor have been widely covered in the literature for decades, but under current classifications, mainly corresponding to the most common presentations of the most frequent type: primary diffuse large B-cell lymphoma of the CNS. Nevertheless, rarer presentations of this specific lymphoma and of other World Health Organization lymphoma subtypes with different imaging features are rarely treated. Moreover, important advances in imaging techniques, changing epidemiologic factors with relevant impact on these tumors (eg, immunodeficiency/dysregulation), and recent updates of the World Health Organization Classification of CNS Tumors 2021 and Hematolymphoid Tumors 2022 may have rendered some accepted concepts outdated. In this article, the authors aim to fulfill a critical need by providing a complete update-review, emphasizing the latest clinical-radiologic features of the full spectrum of lymphomas involving the CNS.

Serum neurofilament levels correlate with electrodiagnostic evidence of axonal loss in paclitaxel-induced peripheral neurotoxicity.

INTRODUCTION: Paclitaxel-induced peripheral neurotoxicity (PIPN) typically manifests as a predominantly sensory axonopathy. Nerve conduction studies (NCS) represent the gold standard method to quantify axonal impairment in PIPN. Serum neurofilament light chain (sNfL) levels are emerging biomarkers for quantifying axonal damage in peripheral neuropathies. To date, the association between NCS abnormalities and sNfL levels during paclitaxel-based chemotherapy has not been specifically addressed. METHODS: We prospectively conducted longitudinal measurement of sNfL levels in 27 chemotherapy-naïve breast cancer patients and correlated conventional NCS recordings with sNfL in 22 of them, before (T0) and after (T1) 12 cycles of weekly paclitaxel-based therapy. RESULTS: PIPN was diagnosed in 24/27 patients (88%) after completion of the 12-week paclitaxel-based chemotherapy regimen. Serum NfL levels (pg/mL) were significantly higher at T1 compared to T0 (T0: 18.50 ± 12.88 vs T1: 255.80 ± 194.16; p < 0.001). The increase of sNfL levels at T1 significantly correlated with the decrease or abolishment of amplitudes recorded from the sural nerve (r = 0.620; p = 0.0035), sensory radial (r = 0.613; p = 0.005), sensory ulnar (r = 0.630; p = 0.005), and peroneal motor (r = 0.568; p = 0.024) nerves. CONCLUSION: sNfL levels proportionally increase during chemotherapy administration and significantly correlate with NCS axonal abnormalities in patients with PIPN. A multimodal testing approach employing both sNfL and NCS might improve the PIPN diagnostic accuracy.

Peripheral neurotoxicity of oxaliplatin in combination with 5-fluorouracil (FOLFOX) or capecitabine (XELOX): a prospective evaluation of 150 colorectal cancer patients.

BACKGROUND: To report our prospective experience on the incidence and pattern of oxaliplatin (OXA)-induced peripheral neuropathy (OXA-IPN) in patients with colorectal cancer (CRC) treated with either FOLFOX-4 or XELoda + OXaliplatin (XELOX). PATIENTS AND METHODS: One hundred and fifty patients scheduled to be treated with either FOLFOX or XELOX for CRC were prospectively monitored at baseline and followed-up during chemotherapy. The incidence and severity of symptoms secondary to OXA-IPN were recorded using three different types of assessment, i.e. the motor and neurosensory National Cancer Institute common toxicity criteria, version 3.0 (NCI-CTCv3), the clinical version of the total neuropathy score (TNSc) and electrophysiological scores. RESULTS: Patients treated with either FOLFOX-4 or XELOX manifested similar incidence rates and severities of acute OXA-IPN. However, FOLFOX-4 was associated with increased incidence of chronic neurotoxicity, compared with XELOX-treated patients (n = 64/77 versus 44/73; P = 0.002), at a very similar OXA median cumulative dose during both regimens. Both the NCI-CTCv3 and TNSc demonstrated that the severity of cumulative OXA-IPN in FOLFOX-4-treated patients is higher than in those treated with XELOX. CONCLUSION: The incidence of acute neurotoxicity during FOLFOX-4 therapy is similar to XELOX. However, it seems that FOLFOX-4 is more neurotoxic than XELOX in terms of cumulative OXA-IPN, despite comparable OXA cumulative dose.

Enhanced survival from CLP-induced sepsis following late administration of low doses of anti-IFNγ F(ab')2 antibody fragments.

OBJECTIVE: To assess the impact of different doses of anti-interferon gamma (anti-IFNγ) F(ab')2 fragments, administered prophylactically, on survival and on serum concentration of cytokines in a murine model of sepsis induced by cecal ligation and puncture (CLP). We further explore the impact of therapeutic administration of the most protective dose on survival. SUBJECTS AND TREATMENT: Balb/c mice were prophylactically treated by the intraperitoneal route with anti-IFNγ initiated 2 h before CLP and every 24 h for a total of five times in each of the following doses: 0.01, 0.1, or 1 mg/kg. Sham and control groups received sterile saline solution in a similar scheme. METHODS: Serum tumor necrosis factor (TNF), interleukin (IL)-1ß, IL-6, IL-10 and IFNγ were measured at 3, 24 and 48 h after CLP by ELISA. Survival curves were compared using a Mantel-Haenzel method. RESULTS: Significant prophylactic protection was found only with 0.01 mg/kg, in association with regulation of IL-1ß and IL-10 concentrations. As therapy, anti-IFNγ fragments were protective only when initiated 24 h after CLP. CONCLUSIONS: Delicate modulation of IFNγ at the correct timing, even when the septic process has begun, is an exciting alternative to explore in the treatment of sepsis.

Usefulness of Video-EEG monitoring in patients with drug-resistant epilepsy.

OBJECTIVE: To evaluate the characteristics of patients on whom long-term Video-EEG monitoring is performed in a specialist centre and to assess its suitability to study refractory epilepsy patients. METHODS: A prospective analysis and study of Video-EEG monitoring was performed in a series of 100 refractory epilepsy patients from a single centre. The analysis included demographic data, the time until the first seizure, the methods used to provoke seizures, and the outcome (usefulness, change in the management, pharmacological and surgical improvement). A subgroup analysis based on diagnosis was performed. RESULTS: The study was performed mainly on young people (mean 34.4 years) and the first seizure appeared in a mean of 30hours, requiring most of the patients to withdraw the medication. Nevertheless, there were no cases of status epilepticus. The usefulness of the test was high in all the groups. The management was changed in 65% of the patients with pharmacological and surgical improvement. CONCLUSION: Long-term Video-EEG monitoring is a suitable test to study refractory epilepsy patients. The main problem in our country is accesibility.

[Nonpalpable testes: laparoscopy for inguinotomy]. / Testículo no palpable: laparoscopia o inguinotomía.

INTRODUCTION: The nonpalpable testis refers to the inability to make objective the teste through exploratory maneuvers. These patients have benefited from the laparoscopic approach that previously they could require even a laparotomy. Definitive treatment of nonpalpable testis depends on the laparoscopic findings, being in dispute their resolution in one or two stages. The aim of this study is to assess the incidence and the results after the application of laparoscopy for the treatment of nonpalpable testis in our department. PATIENTS AND METHODS: All the cases of nonpalpable testis between 2000-2009 are selected. The age of intervention, laterality, operative findings, treatment performed and the size of the testes in cases operated in two stages are analized. RESULTS: Fifty-eight children are reviewed with a total of 60 testis. Thirty-one cases are left (53.4%), 25 are rights (43.1%) and 2 are bilateral (3.5%). In 32 children the testis is absent or atrophic, in 10 the Fowler-Stephens technique is developed, 8 gonads are next to the internal inguinal ring, 5 are in the inguinal canal and 2 is so high and so hipoplasic that orchiectomy is decided. Of those operated in 2 stages, 9 testes survive after the first time and 7 of them have a normal size 6 months after the second surgery. CONCLUSIONS: Laparoscopy is an effective method for diagnosis and treatment of non palpable testis, however, there is still no consensus, for certain locations, to descend the testicle in 1 or 2 stages and if the way is by laparoscopy or inguinotomy.

[Gastroesophageal reflux disease. Evaluation and indication for surgical treatment by esophageal phmetry]. / Enfermedad por reflujo gastroesofágico, Valoración e indicación de tratamiento quirúrgico mediante pHmetría esofágica.

INTRODUCTION: Oesophageal pH monitoring is considered the best procedure to assess the severity of gastroesophageal reflux disease (GERD), conditioning its treatment. The indication for surgery is becoming less common. We intend to meet this test to what extent it has influenced. MATERIAL AND METHODS: We recruit patients treated in our Centre since the introduction of pH monitoring. We compare the number of times before and after its use. We value clinical manifestations, usual pH metric values versus non-operated patients with pathological test, associated pathology. SAMPLE: 91 patients, 151 pH metric studies (98 preoperative). Number of interventions prior to introduction of pH monitoring: 20/year, post: 3.79/year. SYMPTOMS: gastrointestinal 60.2%, respiratory 10.2%, mixed 24.5%. 495 non-operated patients, 692 pathological studies. PH metric values operated/not operated: No. reflux 116.91 +/- 125.46/101.69 +/- 83.39 (p < 0.001), No. reflux >5 minutes 8.49 +/- 8.28/4.43 +/- 4.85 (p = 0.001), longest reflux 60.21 +/- 95.93/31.16 +/- 80.09 (p < 0.001), clearance 1.27 +/- 1.44/0.86 +/- 1.05 (p = 0.04), DeMeester 52.74 +/- 56.21/29.49 +/- 23.57 (p < 0.001). 14 of 98 preoperative pH monitoring were normal. Associated pathology operated/not operated: 13.26%/ 7.47%. CONCLUSIONS: The pH metric control of patients with GERD and the progress of medical treatment have led to a decrease in surgical procedures. In our experience, the intensity of GERD is a valuable parameter in deciding on the surgery. We attach particular value parameters measuring oesophageal clearance and indices that integrate several of them. However, in some patients without pathological pH monitoring, we have indicated the operation. The prevalence of associated pathology in the operated makes us value them more demanding.

Effect of E-beam treatment on expression of virulence and stress-response genes of Listeria monocytogenes in dry-cured ham.

Various adverse conditions can trigger defensive mechanisms in Listeria monocytogenes that can increase the virulence of surviving cells. The objective of this study was to evaluate the expression of one stress-response (sigB) and three virulence (plcA, hly, and iap) genes in L. monocytogenes exposed to a sub lethal dose of E-beam irradiation in dry-cured ham. To accomplish this, dry-cured ham slices (10 g) were immersed in a 109 CFU/mL suspension of L. monocytogenes strain S4-2 and subsequently irradiated with 1, 2, or 3 kGy. After irradiation, samples were stored at 7 °C or 15 °C for 30 days. Absolute gene expression levels were determined by RT-qPCR, and numbers of surviving Listeria cells were assessed by microbial counts after different storage times (0, 7, 15, and 30 days). At 7 °C, after E-beam treatment at doses of 2 or 3 kGy, Listeria gene expression significantly increased (p ≤ 0.05) up to day 15. Listeria counts decreased with increasing dosage. The relationship between absolute gene expression and the number of surviving Listeria cells could indicate that sublethal doses of E-beam irradiation can increase expression of the genes studied. We observed no significant influence of storage time or temperature on gene expression (p > 0.05). Listeria that survives E-beam treatment may display increased virulence, constituting a significant potential public health risk.