Spontaneous bacterial peritoniti: current opportunities of diagnosis and treatment

Departamentul Medicină internă, Catedra Chirurgie 2, USMF „Nicolae Testemiţanu”, Chişinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Actualmente, managementul terapeutic optim al peritonitei bacteriene secundare (PBS) nu reprezintă încă un consens şi continuă să ridice discuţii în ceea ce priveşte tactica terapeutică şi chirurgicală. Material şi metode: Au fost evaluaţi 27 de pacienţi cu PBS dezvoltată pe fondalul cirozei hepatice, care s-au aflat la tratament în perioada 2008-2015, cu vârsta cuprinsă între 25 şi 64 ani. Toţi pacienţii au avut o durată a bolii hepatice cronice peste 5 ani. Regula terapeutică adresată PBS a inclus diagnostic precoce, tratament cu cefalosporine de generaţia a III-a cu toxicitate redusă, tactica expectativă chirurgicală la pacienţii cu evoluţie extrem de gravă şi operaţii minim-invazive ghidate după principiul „primum non nocere”, adresate pacienţilor cu PBS. Rezultate: Paleta de manifestări a fost de la bacterascită asimptomatică până la un sepsis cu o progresie rapidă spre exitus. Cele mai frecvente semne: febra, encefalopatia, durerea abdominală, diareea, ileusul. Douăzeci de pacienţi au fost trataţi medicamentos, în 7 cazuri s-a intervenit chirurgical, în 3 dintre acestea – pe cale minim-invazivă laparoscopică. Evoluţia PBS s-a complicat: cu hemoragie digestivă superioară (3 cazuri), EP (8 cazuri), sindrom hepato-renal (7 cazuri). Letalitatea generală – 9 cazuri (33%), recidiva de PBS – 2 cazuri. Concluzii: Experienţa acumulată ne permite să constatăm că atitudinea interdisciplinară față de PBS este justificată şi absolut necesară: echipa instruită compusă din hepatolog/gastroenterolog, reanimatolog, endoscopist şi chirurg este indispensabilă.Introduction: At present, the optimal therapeutic management of secondary bacterial peritonitis (SBP) does not reach yet a consensus and continue to rise the discussion regarding the therapy and surgery. Material and methods: Twenty seven patients (aged between 25 and 64 years) with SBP developed on the basis of liver cirrhosis, treated during 2008-2015 were evaluated. All patients had chronic liver disease lasting more than 5 years. Therapeutic approach addressed SBP included: early diagnosis, treatment with third generation of cephalosporins with low toxicity, using of expecting surgical tactics in patients with extremely severe condition and minimally invasive operations guided by the principle of „primum non nocere” to patients with SBP. Results: The manifestations varied from asymptomatic bacterial ascytis up to a sepsis with rapid progression to death. The most common signs were: fever, encephalopathy, abdominal pain, diarrhea, and ileus. Twenty patients were treated medically, surgery was performed in 7 cases, 3 of them – minimally invasive laparoscopic. SBP evolution was complicated with upper digestive bleeding (3 cases), EP (8 cases), hepato-renal syndrome – (7 cases). General mortality was – 9 cases (33%), recurrent SBP – 2 cases. Conclusions: The experience allows us to conclude that SBP obligatory requires the interdisciplinary approach as well as trained team composed from hepatologist / gastroenterologist, reanimatologist, endoscopist and the surgeon

PHOTOVOLTAIC PRODUCTION MANAGEMENT IN STOCHASTIC OPTIMIZED MICROGRIDS

The microgrids are composed of small scale fueled generation capacities, renewable energy sources, storage energy systems, controllable loads, and autonomously can connect or disconnect from the mains supply. The microgrids can operate connected to the upstream main grid, or in an islanded operation mode following a large perturbation in the upstream grid. The microgrid analyzed in this paper is composed of a photovoltaic system, a thermal engine, an electrochemical storage system, critical and interruptible loads. As backup generation is considered a classical generation engine and a small scale storage unit. The autonomous switching between grid-connected and islanding operation modes can occur, under an excess/deficit of generation and function of the electricity market price. The paper deals with an optimization model for minimizing the microgrid operation costs under intermittent generation and variable demand function of microgrid operation constrains. The optimization model is tested on a 24 hours horizon. The gridconnected optimized operation accounts also the exchanged power with the upstream grid function of the electricity price within the public network

Assessment of portal hemodinamics in patients with liver cirrhosis, treated surgically

Catedra radiologie şi imagistică medicală, Departamentul medicină internă, Catedra 2 Chirurgie, USMF „Nicolae Testemiţanu”, Chişinău, Republica Moldova, Al XII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” din Republica Moldova cu participare internațională 23-25 septembrie 2015Introducere: Dezvoltarea tehnicilor imagistice a adus o contribuţie importantă în cunoaşterea complexităţii tulburărilor hemodinamicii portale (HDP) generate de afectarea hepatică cronică. Scopul lucrării este evaluarea imagistică eco-Doppler şi analiza comparativă a parametrilor HDP la pacienţii cu ciroză hepatică trataţi chirurgical. Material şi metode: Într-un lot de 111 pacienţi cirotici trataţi chirurgical cu vărsta între 19 şi 47 ani, s-a evaluat gradul de severitate a modificărilor HDP studiat prin ecografie Doppler duplex color cu aprecierea parametrilor cantitativi atât pe versantul arterial, cât şi pe cel venos. Evaluarea severităţii cirozei hepatice a fost apreciată conform clasificării de prognostic Child-Pugh. Rezultate: Preoperator a fost stabilită o corelare importantă a hipersplenismului cu majorarea rezistenţei vasculare la nivelul arterei lienale (r=0,454, Se 79%, Sp 69%, RP +2,5), iar indicele splenoportal a crescut evident paralel cu avansarea sindromului de hipersplenism (r=0,516). Scorul Child corelează puternic cu gradele de severitate a dereglărilor HDP evaluate imagistic. După tratamentul chirurgical se atestă o micşorare a diametrului venei porte şi a fluxului portal, iar fluxul la nivelul arterei hepatice denotă o creştere în paralel cu diminuarea rezistenţei vasculare la acest nivel (p<0,001). Concluzii: Rezultatele obținute prin evaluarea imagistică a HDP trebuie interpretate în context clinic, biologic şi morfologic. Utilizarea unui algoritm care ar asocia parametrii enunţaţi poate reprezenta metoda optimă de stadializare şi monitorizare a tulburărilor HDP.Introduction: The development of imaging techniques has made an important contribution to knowledge of the complexity of portal haemodynamic (PH) disorders caused by chronic liver disease. The purpose of study was the eco-Doppler imaging assessment and comparative analysis of PH parameters in patients with liver cirrhosis treated surgically. Material and methods: In a group of 111 cirrhotic patients treated surgically with age between 19 and 47 years, the severity of PH disturbances was evaluated by color Doppler duplex ultrasound with quantitative analysis of the characteristics of arterial and venous blood flow. Liver cirrhosis severity was assessed and graded according to Child-Pugh prognostic classification. Results: Preoperative was established significant hypersplenism with increasing of vascular resistance in splenic artery (r=0.454, Se 79%, Sp 69%, RP +2.5) and splenoportal index increase obvious parallel with advancing of hypersplenism syndrome (r=0.516). Child score strongly correlates with the degree of severity of PH disturbances rated by imaging. After surgery there was a reduction in the diameter of the portal vein and portal flow and hepatic artery flow shows an increase in parallel with the decrease of vascular resistance at this level (p<0.001). Conclusions: The results of the imaging assessment of PH must be interpreted in clinical, biological and morphological context. Utilization of an algorithm that can associate above mentioned parameters could optimize the staging and monitoring of PH disorders

Оценка противовирусной терапии у больных с циррозом печени вирусной этиологии C и D

Summary: Study group: 49 patients, 17 (34.69%) women and 32 (65.31%) men with hepatic viral cirrhosis, Child-Pugh stage A: 24 – D viral etiology and 25 – viral C genesis. Average age: 44.41 ± 0.4 years in women and 47.59 ± 0.6 years in men. Purpose: evaluation of the antiviral treatment response at 12 weeks and 24 weeks after initiation and assessment of laboratory results during antiviral therapy in patients with liver cirrhosis C and D. In patients with liver cirrhosis HDV, treated with Peg-INF undetectable viral load was achieved at 12 weeks in 28% cases and after 24 weeks of treatment it is observed in 25% of cases. In the group of patients with liver cirrhosis HCV, treated with Peg-INF + Ribabirină – 12 weeks of treatment – 75% of patients responded positively: 48% achieved complete EVR and 24% – EVR part. Evaluation of patients at 24 weeks of treatment show a positive virologic response in 56% cases. In patients with liver cirrhosis HCV and HDV, where the virological response was absent, more severe, and early complications of antiviral therapy are observed: the blood count shows anemia, major leukopenia and thrombocytopenia.Pезюме: Группа исследования: 49 пациентов, 17 (34,69%) женщин и 32 (65,31%) мужчин с циррозом печени вирусной этиологии, стадия Child-Pugh А: 24 – вирусной этиологии D и 25 – вирусной этиологии C. Средний возраст: 44,41 ± 0,4 лет у женщин и 47,59 ± 0,6 лет у мужчин. Цель: оценка ответа на противовирусное лечение на 12-ой неделе и на 24-ой неделе после начала лечения и оценка лабораторных показателей во время противовирусной терапии у больных с циррозом печени С или D. У пациентов с циррозом печени HDV, леченных Peg-INF, была достигнута авиремия на 12-ой неделе в 28% случаев и на 24-ой неделе лечения – в 25% случаев. В группе пациентов с циррозом печени вирусной этиологии С, леченных Peg-INF + рибавирин, наблюдается на 12-ой неделе лечения положительный ответ у 75% пациентов: у 48% достигнут полный ранний вирусологический ответ, у 24% – частичный. Оценка противовирусного лечения через 24 недели после начала показала положительный вирусологический ответ в 56% случаев. У пациентов с циррозом печени вирусной этиологии С или D с отсутствием вирусологического ответа на противирусную терапию обнаруживаются осложнения более тяжелые и раньше: в анализе крови – анемия, лейкопения и тромбоцитопения

A dinosaurian facial deformity and the first occurrence of ameloblastoma in the fossil record

Despite documentation of various types of neoplastic pathologies encountered in the vertebrate fossil record, no ameloblastic tumours have been recognised so far. Ameloblastoma is a benign neoplasic tumour with a strong preponderance for the mandible. Here, we report for the first time the presence of an ameloblastoma neoplasm in the lower jaw of a specimen referred to the derived non-hadrosaurid hadrosauroid dinosaur Telmatosaurus transsylvanicus from the uppermost Cretaceous of the Haeg Basin in Romania. The location, external appearance and internal structure of the pathological outgrowth provide clear evidence for the diagnosis of ameloblastoma in Telmatosaurus. This report extends the range of pathologies encountered in hadrosauroid dinosaurs. In addition, recognition of an ameloblastoma neoplasm in a taxon lying close to the origin of ‘duck-billed’ hadrosaurid dinosaurs confirms the predisposition of this clade towards neoplasia pathologies already in its basal members

Chemotherapy in patients with unresected pancreatic cancer in Australia: A population-based study of uptake and survival

1 Aim Palliative chemotherapy improves symptom control and prolongs survival in patients with unresectable pancreatic cancer, but there is a paucity of data describing its use and effectiveness in everyday practice. We explored patterns of chemotherapy use in patients with unresected pancreatic cancer in Australia and the impact of use on survival. 2 Methods We reviewed the medical records of residents of New South Wales or Queensland, Australia, diagnosed with unresectable pancreatic adenocarcinoma between July 2009 and June 2011. Associations between receipt of chemotherapy and sociodemographic, clinical and health service factors were evaluated using logistic regression. We used Cox proportional hazards models to analyze associations between chemotherapy use and survival. 3 Results Data were collected for 1173 eligible patients. Chemotherapy was received by 44% (n = 184/414) of patients with localized pancreatic cancer and 53% (n = 406/759) of patients with metastases. Chemotherapy receipt depended on clinical factors, such as performance status and comorbidity burden, and nonclinical factors, such as age, place of residence, multidisciplinary team review and the type of specialist first encountered. Consultation with an oncologist mitigated most of the sociodemographic and service‐related disparities in chemotherapy use. The receipt of chemotherapy was associated with prolonged survival in patients with inoperable pancreatic cancer, including after adjusting for common prognostic factors. 4 Conclusions These findings highlight the need to establish referral pathways to ensure that all patients have the opportunity to discuss treatment options with a medical oncologist. This is particularly relevant for health care systems covering areas with a geographically dispersed population

474 Phase 1 study of SEA-TGT, a human, nonfucosylated anti-TIGIT monoclonal antibody with enhanced immune-effector function, in patients with advanced malignancies (SGNTGT-001, trial in progress)

BackgroundT-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory domains (TIGIT), and costimulatory receptor CD226 competitively bind 2 ligands, CD155 and CD112, which are expressed by tumor cells and antigen-presenting cells in the tumor microenvironment.1 2 Dual TIGIT/programmed cell death protein-1 (PD-1) blockade increased tumor antigen-specific CD8+ T-cell expansion and function in vitro and promoted potent antitumor response in vivo.3 4 TIGIT/PD-1 dual blockade using a TIGIT monoclonal antibody (mAb) with intact Fc produced clinical responses in advanced cancer.5 SEA-TGT is an investigational, human, nonfucosylated mAb directed against TIGIT. SEA-TGT binds to TIGIT, blocking inhibitory checkpoint signals directed at T cells. SEA-TGT enhances binding to activating FcγRIIIa and decreases binding to inhibitory FcγRIIb; this depletes immunosuppressive regulatory T cells and amplifies naive and memory T cells, potentially augmenting PD-1 inhibition effects. Preclinically, at suboptimal doses, SEA-TGT plus anti-PD-1 mAbs had superior antitumor activity than either agent alone.6MethodsSafety and antitumor activity of SEA TGT in ~377 adults (≥18 years) will be evaluated in this phase 1, multicenter, open-label, dose-escalation/expansion study. Part A will assess the safety/tolerability of SEA TGT to determine maximum tolerated and recommended doses. Part B will assess the safety and antitumor activity of the recommended dose in disease-specific expansion cohorts. Part C will assess SEA-TGT plus sasanlimab in dose-expansion cohorts after an initial safety run-in. Patients with histologically/cytologically confirmed relapsed/refractory/progressive metastatic solid tumors including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), gastric/gastroesophageal junction carcinoma, cutaneous melanoma, bladder, cervical, ovarian or triple-negative breast cancer, or selected lymphomas will be eligible for Parts A and B. Part C will enroll patients with histologically confirmed advanced NSCLC (high [tumor proportion score (TPS) ≥50%] and low [TPS=1–49%] PD ligand 1 [PD-L1] expression), cutaneous melanoma, and HNSCC without previous anti–PD-1/PD-L1 therapy exposure. SEA TGT will be administered on Day 1 of 21-day cycles.Laboratory abnormalities, adverse events, dose-limiting toxicities, and dose-level safety and activity are primary endpoints. Secondary endpoints are objective response (OR) and complete response (CR) rates, duration of OR/CR, progression-free survival, overall survival, pharmacokinetics (PK), and antidrug antibodies. Exploratory analysis will include pharmacodynamics (PD), PK/PD relationships, biomarkers, and resistance to SEA-TGT. This trial is recruiting in Europe and North America.Trial RegistrationNCT04254107ReferencesBlake SJ, Dougall WC, Miles JJ, et al. Molecular pathways: Targeting CD96 and TIGIT for cancer immunotherapy. Clin Cancer Res 2016;22(21):5183–5188.Chauvin JM, Zarour HM. TIGIT in cancer immunotherapy. J ImmunoTher Cancer 2020;8:e000957.Johnston RJ, Comps-Agrar L, Hackney J, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. Cancer Cell 2014;26(6):923–937.Chauvin JM, Pagliano O, Fourcade J, et al. TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients. J Clin Invest 2015;125(5):2046–2058.Rodriguez-Abreu D, Johnson ML, Hussein MA, et al. Primary analysis of a randomized, double-blind, phase 2 study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE). J Clin Oncol 2020;38(15 suppl):9503.Smith A, Zeng W, Lucas S, et al. Poster 1583. SEA-TGT is an empowered anti-TIGIT antibody that displays superior combinatorial activity with several therapeutic agents. Presented at: American Association for Cancer Research Annual Meeting; April 9–14, 2021; Virtual Meeting.Ethics ApprovalInstitutional review boards or independent ethics committees of participating sites approved the trial, which will be conducted in compliance with the Declaration of Helsinki and International Conference on Harmonisation Guidelines for Good Clinical Practice. All patients will provide written informed consent

Measurement and determination of encoder disc surface parameters in x-z planes using a conventional optical disc reading head

Non-contact surface measurement methods as well as roughness parameter determination methods are analyzed in the paper. While most of the modern non-contact surface inspection methods require advanced instrumentation and a big budget, this study looks into a novel approach to non-contact encoder disc roughness measurements by using the proposed system attached to the rotary table with an implemented optical disc pick up head and the reference angle encoder. Application of a conventional optical disc laser reading system resulted in a cost effective and compact solution for a non-destructive angle encoder disc surface inspection. Assets and shortcomings as well as detailed analysis of the measurement procedure are explained in the paper. The experimental setup and the measurement results are presented within this article

Precision Oncology Decision Support: Current Approaches and Strategies for the Future

With the increasing availability of genomics, routine analysis of advanced cancers is now feasible. Treatment selection is frequently guided by the molecular characteristics of a patient\u27s tumor, and an increasing number of trials are genomically selected. Furthermore, multiple studies have demonstrated the benefit of therapies that are chosen based upon the molecular profile of a tumor. However, the rapid evolution of genomic testing platforms and emergence of new technologies make interpreting molecular testing reports more challenging. More sophisticated precision oncology decision support services are essential. This review outlines existing tools available for health care providers and precision oncology teams and highlights strategies for optimizing decision support. Specific attention is given to the assays currently available for molecular testing, as well as considerations for interpreting alteration information. This article also discusses strategies for identifying and matching patients to clinical trials, current challenges, and proposals for future development of precision oncology decision support

Phase I Study of mTORC1/2 Inhibitor Sapanisertib (CB-228/TAK-228) in Combination with Metformin in Patients with mTOR/AKT/PI3K Pathway Alterations and Advanced Solid Malignancies

BACKGROUND: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of 5\u27-AMP-activated protein kinase (AMPK) suggesting combination therapy may enhance antitumor activity of sapanisertib. We report preliminary safety, tolerability, and efficacy from the dose-escalation study of sapanisertib in combination with metformin in patients with advanced solid tumors. METHODS: Patients with advanced metastatic solid tumors resistant or refractory to standard treatment, with and without mTOR/AKT/PI3K pathway alterations, received sapanisertib 3 or 4 mg daily together with metformin once to three times daily (500-1,500 mg). All patients underwent 14-day titration period for metformin in cycle 1. Tumor measurements were performed following cycle 2 and subsequently every 8 weeks. RESULTS: A total of 30 patients were enrolled across four cohorts (3 mg/500 mg; 3 mg/1,000 mg, 4 mg/1,000 mg; 4 mg/1,500 mg). 19 were female (63%), median age was 57 (range: 30-77), all were Eastern Cooperative Oncology Group performance status 1. Tumor types included sarcoma (6), breast (4), ovarian (4), head and neck (3), colorectal (2), lung (2), renal cell (2), endometrial (2), gastroesophageal junction (1), prostate (1), stomach (1), urachus (1), and cervical cancer (1). Median number of prior lines of therapy was 4. Most common genomic alterations included PIK3CA (27%), PTEN (17%), AKT1/2 (10%), mTOR (10%). Of 30 patients evaluable for response, 4 patients achieved partial response (PR); 15 patients achieved stable disease (SD) as best response. Disease control rate (PR+SD) was 63%. Of the responders in PR, 3 of 4 patients had documented PTEN mutations (3/5 patients enrolled with PTEN mutations had PR); 2 of 4 of patients in PR had comutations (patient with leiomyosarcoma had both PTEN and TSC; patient with breast cancer had both PTEN and STK11); 1 of 4 patients in PR had AKT and mTOR mutation; tumor types included leiomyosarcoma (n = 2), breast (n = 1), and endometrial cancer (n = 1). Most common treatment-emergent adverse events included nausea, anorexia, diarrhea, and rash. Grade (G) 3-5 treatment-related adverse events included hyperglycemia (4/30; 13%), fatigue (2/30; 7%), hypertriglyceridemia (1/30; 3%), rash (2/20; 7%), diarrhea (2/30; 7%), creatinine increase (1/30; 3%), acidosis (1/30; 3%). No dose-limiting toxicities (DLT) were reported in the 3 mg/500 mg cohort. One of 6 patient had DLT in the 3 mg/1,000 mg cohort (G3 diarrhea) and 2 of 11 patients had DLTs in the 4 mg/1,500 mg cohort (G3 fatigue, G3 rash). 4 mg/1,000 mg was defined as the MTD. CONCLUSIONS: The safety profile of mTORC1/2 inhibitor sapanisertib in combination with metformin was generally tolerable, with antitumor activity observed in patients with advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations. SIGNIFICANCE: Sapanisertib (CB-228/TAK-228) is a potent, selective ATP-competitive, next-generation dual inhibitor of mTORC1/2. Metformin is thought to inhibit the mTOR pathway through upstream activation of AMPK suggesting combination therapy may enhance antitumor activity of sapanisertib. This dose-escalation study of sapanisertib and metformin in advanced solid tumors and mTOR/AKT/PI3K pathway alterations, demonstrates safety, tolerability, and early clinical activity in advanced malignancies harboring PTEN mutations and AKT/mTOR pathway alterations.Clinical trial information: NCT03017833