Determination of the HER2 amplification status by in situ fluorescent hybridization and concordance with immunohistochemistry for breast cancer samples in Colombia

Objectives:

To determine the status of the HER2 amplification in Breast cancer performed in peripheral laboratories in Colombia by immunohistochemistry and its comparison with central laboratories and the FISH status.

Methods:

Four thousand one hundred and five cases referred for the determination of the HER2 status by FISH and/or IHQ to the Department of Pathology of the Fundacion Santa Fe were studied. The analysis included correlation between the IHQ HER2 score submitted by the peripheral laboratory (PL), the HER2 score emitted in the CL and the FISH studies performed in the central laboratory (CL).

Results:

Two thousand five hundred and eight HER2 IHQ studies were performed in the (CL), using the Dako Herceptest. With the following results: 68.2 % negative (0-1+); 16,4% indeterminate (2+); 15.3% 3+ and 2.3 % not adequate. 1360/ 1719 cases studied by FISH came from the (PL), and 329 (19.1%) from the (CL). Comparing the IHQ score emitted by the PL and the positive FISH status showed: 6/28 0+ were positive (21. 4%); 7/31 1+ (22. 5%); 397/1240 2+ (32.8%) and 74/91 3+ (81. 3%). In the CL the results were 1/9 0+ (11.1%); 3/18 1+ (16.7%); 154/292 2+ (53%); and 9/9 3+ (100%). Only 1/4 negative cases (0/1+) was in house.

Conclusion:

The false negative rate (22%), and false positive results (18.7%), of the HER2 status performed by IHQ in peripheral laboratories in Colombia is unacceptable high as well as the inadequacy of tissue indicating that pre-analytical factors have to be improved in Colombia in order to get optimal results.     

A Novel Regulatory Defect in the Branched‐Chain α‐Keto Acid Dehydrogenase Complex Due to a Mutation in the PPM1K Gene Causes a Mild Variant Phenotype of Maple Syrup Urine Disease

This article describes a hitherto unreported involvement of the phosphatase PP2Cm, a recently described member of the branched‐chain α‐keto acid dehydrogenase (BCKDH) complex, in maple syrup urine disease (MSUD). The disease‐causing mutation was identified in a patient with a mild variant phenotype, involving a gene not previously associated with MSUD. SNP array‐based genotyping showed a copy‐neutral homozygous pattern for chromosome 4 compatible with uniparental isodisomy. Mutation analysis of the candidate gene, PPM1K, revealed a homozygous c.417_418delTA change predicted to result in a truncated, unstable protein. No PP2Cm mutant protein was detected in immunocytochemical or Western blot expression analyses. The transient expression of wild‐type PPM1K in PP2Cm‐deficient fibroblasts recovered 35% of normal BCKDH activity. As PP2Cm has been described essential for cell survival, apoptosis and metabolism, the impact of its deficiency on specific metabolic stress variables was evaluated in PP2Cm‐deficient fibroblasts. Increases were seen in ROS levels along with the activation of specific stress‐signaling MAP kinases. Similar to that described for the pyruvate dehydrogenase complex, a defect in the regulation of BCKDH caused the aberrant metabolism of its substrate, contributing to the patient's MSUD phenotype—and perhaps others.     

The safety and efficacy of pembrolizumab for the treatment of non-small cell lung cancer

ABSTRACT

Introduction: Lung cancer is the leading cancer-related cause of death worldwide. The introduction of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has significantly improved the outcome of these patients. Pembrolizumab, a monoclonal IgG4-kappa antibody against programmed-death-1 (PD-1) protein, nowadays represents a standard of care for NSCLC patients. Although it has a favorable toxicity profile, some immune-related adverse events (irAEs) can be life-threatening, therefore its knowledge may help to optimize the care of these patients.

Areas covered: The authors review data regarding the efficacy and safety of pembrolizumab from the most relevant clinical trials as well as toxicities reported in the clinical use. Special considerations of use in special populations will be noted. Finally, its toxicity profile will be compared with other ICIs used in NSCLC.

Expert opinion: In the scenario of NSCLC, pembrolizumab shows a favorable safety profile with less than 10% serious immune-related adverse events (irAEs) when used in monotherapy and without adding relevant extra-toxicity to chemotherapy when used in combination. Monotherapy with pembrolizumab is associated with better health-related quality of life than chemotherapy. Early recognition and appropriate treatment of irAEs is of prime importance as most are reversible if correctly managed. Rechallenge with pembrolizumab is frequently feasible.     

PET/TC con 18F-FDG en la sospecha de infección asociada a dispositivos intracardiacos: rendimiento y utilidad diagnóstica

Introduction and objectivesCardiac device-related infections (CDRI) may be life-threatening and require early and accurate diagnosis. The aims of this study were to analyze the performance of positron emission tomography-computed tomography (PET/CT) in suspected CDRI, to assess changes to the initial diagnosis, and to identify a clinical subgroup deriving the greatest benefit from this imaging modality.MethodsRetrospective study including patients evaluated by PET/CT for suspected CDRI from 2011 to 2018. We assessed PET/CT performance and the agreement between the initial, post-PET and definitive diagnoses. We also assessed changes in the diagnosis, depending on initial clinical suspicion, to identify patients deriving the greatest benefit from PET/CT.ResultsWe included 44 patients. The prevalence of endocarditis was 57%. The sensitivity and specificity of PET/CT for the diagnosis of infective endocarditis were 0.84 and 0.95, respectively. Post-PET diagnosis improved the initial diagnosis by 45%. PET/CT correctly reclassified 57% of patients with initial suspicion of generator pocket infection by detecting lead infection.ConclusionsPET/CT showed high diagnostic performance in suspected of CDRI and significantly improved the conventional diagnostic approach, especially in patients with initial suspicion of focal infection.     

Humidification during laparoscopic surgery: overview of the clinical benefits of using humidified gas during laparoscopic surgery

Purpose

The peritoneum is the serous membrane that covers the abdominal cavity and most of the intra-abdominal organs. It is a very delicate layer highly susceptible to damage and it is not designed to cope with variable conditions such as the dry and cold carbon dioxide (CO₂) during laparoscopic surgery. The aim of this review was to evaluate the effects caused by insufflating dry and cold gas into the abdominal cavity after laparoscopic surgery.

Methods

A literature search using the Pubmed was carried out. Articles identified focused on the key issues of laparoscopy, peritoneum, morphology, pneumoperitoneum, humidity, body temperature, pain, recovery time, post-operative adhesions and lens fogging.

Results

Insufflating dry and cold CO₂ into the abdomen causes peritoneal damage, post-operative pain, hypothermia and post-operative adhesions. Using humidified and warm gas prevents pain after surgery. With regard to hypothermia due to desiccation, it can be fully prevented using humidified and warm gas. Results relating to the patient recovery are still controversial.

Conclusions

The use of humidified and warm insufflation gas offers a significant clinical benefit to the patient, creating a more physiologic peritoneal environment and reducing the post-operative pain and hypothermia. In animal models, although humidified and warm gas reduces post-operative adhesions, humidified gas at 32 °C reduced them even more. It is clear that humidified gas should be used during laparoscopic surgery; however, a question remains unanswered: to achieve even greater clinical benefit to the patient, at what temperature should the humidified gas be when insufflated into the abdomen? More clinical trials should be performed to resolve this query.

     

C-reactive protein levels and survival in patients with moderate to very severe COPD

BACKGROUND: Serum levels of C-reactive protein (CRP) are increased in patients with COPD and correlate modestly with variables predictive of outcomes. In epidemiologic studies, CRP level is associated with all-cause mortality in patients with mild-to-moderate disease. OBJECTIVE: To determine if CRP levels are associated with survival in patients with moderate to very severe COPD in comparison with other well-known prognostic parameters of the disease. METHODS: In 218 stable patients with COPD, we measured baseline serum CRP level, BODE (body mass index, obstruction, dyspnea, and exercise capacity) index and its components, arterial oxygenation (Pao(2)), inspiratory capacity (IC) to total lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the patients over time and evaluated the strength of the association between the variables and all-cause mortality. RESULTS: During the follow-up time (median, 36 months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP levels were similar between survivors and the deceased (median, 3.8 mg/L; 95% confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval, 2.1 to 11.5; p = 0.22) and was not significantly associated with survival. CONCLUSIONS: In this population of patients with clinically moderate to very severe COPD, the level of CRP level was not associated with survival compared with other prognostic clinical tools such as the BODE index, modified Medical Research Council scale, 6-min walk distance, percentage of predicted FEV(1), IC/TLC ratio < 0.25, and Pao(2). Other long-term studies of well-characterized patients with COPD could help determine the exact role of CRP levels as a biomarker in patients with clinical COPD.     

Periodontitis in Rats Induces Systemic Oxidative Stress That Is Controlled by Bone‐Targeted Antiresorptives

Background: Periodontitis is a chronic, polymicrobial inflammatory disease that degrades connective tissue and alveolar bone and results in tooth loss. Oxidative stress has been linked to the onset of periodontal tissue breakdown and systemic inflammation, and the success of antiresorptive treatments will rely on how effectively they can ameliorate periodontal disease–induced oxidative stress during oral infection. Methods: Rats were infected with polybacterial inoculum consisting of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, as an oral lavage every other week for 12 weeks. Daily subcutaneous injections of enoxacin, bis‐enoxacin, alendronate, or doxycycline were administered for 6 weeks after 6 weeks of polybacterial infection in rats. The serum levels of oxidative stress parameters and antioxidant enzymes, including glutathione peroxidase, superoxide dismutase, and catalase, were evaluated in each of the infected, treated, and sham‐infected rats. Results: Rats infected with the periodontal pathogens displayed a five‐fold increase in the oxidative stress index compared with controls as a result of increased levels of serum oxidants and decreases in total antioxidant activity. The overall decrease in antioxidant activity occurred despite increases in three important antioxidant enzymes, suggesting an imbalance between antioxidant macromolecules/small molecules production and antioxidant enzyme levels. Surprisingly, the bone‐targeted antiresorptives bis‐enoxacin and alendronate inhibited increases in oxidative stress caused by periodontitis. Bis‐enoxacin, which has both antiresorptive and antibiotic activities, was more effective than alendronate, which acts only as an antiresorptive. Conclusion: To the best of the authors’ knowledge, this is the first study to demonstrate that the increased oxidative stress induced by periodontal infection in rats can be ameliorated by bone‐targeted antiresorptives.     

Extra-abdominal infections due to Gemella species.

OBJECTIVES: To understand the role of Gemella species as a pathogen causing extra-abdominal infections in the Hospital General Universitario Gregorio Mara?ón. MATERIALS AND METHODS: Between 1994 and 1998, one or more isolates of Gemella sp. were found in 128 patients. The 113 patients with isolates from nonsignificant specimens or representing intra-abdominal infections were excluded. The clinical records of the remaining 15 patients were reviewed as well as the more recent literature. RESULTS: Mean age of patients was 41 years. The underlying conditions most frequently noted were intravenous drug users (n=6; 3 positive for human immunodeficiency virus), alcoholism (n=2), cardiovascular disease (n=2), chronic lung disease (n=2), diabetes (n=1), kidney transplant (n=1). The extra-abdominal infections were skin and soft tissue abscess (n=5), empyema (n=4), brain abscess (n=2), primary bacteremia (n=1), lung abscess (n=1), septic thrombophlebitis (n=1), complicated urinary tract infection (n=1). The infection was monomicrobial in six and polymicrobial in nine cases. Surgical drainage and betalactam antibiotics were used. The outcome was favorable in almost all cases. CONCLUSIONS: Gemella sp. should be included as a cause of localized soft-tissue abscesses, empyema, and bloodstream infection. No case of infective endocarditis was found. Although it is susceptible to several antibiotics, Gemella sp. requires a careful microbiologic diagnosis and a subtle clinical interpretation.