Zespół pieczenia jamy ustnej

  Zespół pieczenia jamy ustnej (BMS) jest idiopatyczną jednostką chorobową manifestującą się jako długotrwałe uczucie piekącego, palącego lub kłującego bólu w obrębie błon śluzowych jamy ustnej, najczęściej języka. Dolegliwościom bólowym często towarzyszą zaburzenia smaku, uczucie suchości jamy ustnej oraz nieprawidłowości psychiatryczne. Mimo że jest to stosunkowo częste schorzenie, szczególnie w przypadku kobiet w wieku pomenopauzalnym, a jego obraz kliniczny opisuje się w literaturze medycznej od niemal 150 lat, BMS nadal stanowi mało znany problem diagnostyczny i terapeutyczny. Trudności napotykane w praktyce klinicznej są w dużej mierze wynikiem słabo poznanej, wieloczynnikowej etiologii schorzenia, nieobecnością żadnych nieprawidłowości w zakresie morfologii błon śluzowych jamy ustnej oraz niedostatkiem randomizowanych badań weryfikujących skuteczność postępowania leczniczego. Celem tego artykułu jest przybliżenie czytelnikom typowego obrazu klinicznego BMS, ukazanie znaczenia diagnostyki różnicowej zespołu oraz przedstawienie aktualnych danych dotyczących dostępnych sposobów terapii. Znajomość powyższych kwestii przez lekarzy różnych specjalności jest kluczowa dla poprawy jakości życia pacjentów cierpiących na BMS.

Adenoid cystic carcinoma: emerging role of translocations and gene fusions.

Adenoid cystic carcinoma (ACC), the second most common salivary gland malignancy, is notorious for poor prognosis, which reflects the propensity of ACC to progress to clinically advanced metastatic disease. Due to high long-term mortality and lack of effective systemic treatment, the slow-growing but aggressive ACC poses a particular challenge in head and neck oncology. Despite the advancements in cancer genomics, up until recently relatively few genetic alterations critical to the ACC development have been recognized. Although the specific chromosomal translocations resulting in MYB-NFIB fusions provide insight into the ACC pathogenesis and represent attractive diagnostic and therapeutic targets, their clinical significance is unclear, and a substantial subset of ACCs do not harbor the MYB-NFIB translocation. Strategies based on detection of newly described genetic events (such as MYB activating super-enhancer translocations and alterations affecting another member of MYB transcription factor family-MYBL1) offer new hope for improved risk assessment, therapeutic intervention and tumor surveillance. However, the impact of these approaches is still limited by an incomplete understanding of the ACC biology, and the manner by which these alterations initiate and drive ACC remains to be delineated. This manuscript summarizes the current status of gene fusions and other driver genetic alterations in ACC pathogenesis and discusses new therapeutic strategies stemming from the current research

Winter Bird Assemblages in Rural and Urban Environments: A National Survey

Urban development has a marked effect on the ecological and behavioural traits of many living organisms, including birds. In this paper, we analysed differences in the numbers of wintering birds between rural and urban areas in Poland. We also analysed species richness and abundance in relation to longitude, latitude, human population size, and landscape structure. All these parameters were analysed using modern statistical techniques incorporating species detectability. We counted birds in 156 squares (0.25 km2 each) in December 2012 and again in January 2013 in locations in and around 26 urban areas across Poland (in each urban area we surveyed 3 squares and 3 squares in nearby rural areas). The influence of twelve potential environmental variables on species abundance and richness was assessed with Generalized Linear Mixed Models, Principal Components and Detrended Correspondence Analyses. Totals of 72 bird species and 89,710 individual birds were recorded in this study. On average (±SE) 13.3 ± 0.3 species and 288 ± 14 individuals were recorded in each square in each survey. A formal comparison of rural and urban areas revealed that 27 species had a significant preference; 17 to rural areas and 10 to urban areas. Moreover, overall abundance in urban areas was more than double that of rural areas. There was almost a complete separation of rural and urban bird communities. Significantly more birds and more bird species were recorded in January compared to December. We conclude that differences between rural and urban areas in terms of winter conditions and the availability of resources are reflected in different bird communities in the two environments

Metronomic Chemotherapy in Prostate Cancer

Despite the significant expansion of the therapeutic armamentarium associated with the introduction of novel endocrine therapies, cytotoxic agents, radiopharmaceuticals, and PARP inhibitors, progression of metastatic castration-resistant prostate cancer (mCRPC) beyond treatment options remains the leading cause of death in advanced prostate cancer patients. Metronomic chemotherapy (MC) is an old concept of wise utilization of cytotoxic agents administered continuously and at low doses. The metronomic is unique due to its multidimensional mechanisms of action involving: (i) inhibition of cancer cell proliferation, (ii) inhibition of angiogenesis, (iii) mitigation of tumor-related immunosuppression, (iv) impairment of cancer stem cell functions, and (v) modulation of tumor and host microbiome. MC has been extensively studied in advanced prostate cancer before the advent of novel therapies, and its actual activity in contemporary, heavily pretreated mCRPC patients is unknown. We have conducted a prospective analysis of consecutive cases of mCRPC patients who failed all available standard therapies to find the optimal MC regimen for phase II studies. The metronomic combination of weekly paclitaxel 60 mg/m2 i.v. with capecitabine 1500 mg/d p.o. and cyclophosphamide 50 mg/d p.o. was selected as the preferred regimen for a planned phase II study in heavily pretreated mCRPC patients

Ocena skuteczności chemioterapii z zastosowaniem kapecytabiny i oksaliplatyny u chorych na uogólnionego raka jelita grubego. Wpływ lokalizacji ogniska pierwotnego raka na skuteczność leczenia

Wstęp. Rak jelita grubego jest coraz częstszym nowotworem, a dzięki możliwości stosowania wielu leków oraz terapii skojarzonej nosi znamiona choroby przewlekłej. Istotne znaczenie ma poprawa jakości życia chorych.  Materiał i metody. Niniejsza analiza dotyczy schematu opartego na oksaliplatynie i kapecytabinie (CAPOX), użytego w grupie 305 chorych. Chemioterapię tę zastosowano w ramach I, II lub III linii leczenia paliatywnego.  Wyniki. W pracy udowodniono skuteczność schematu mimo redukcji dawek leków u około 50% chorych, a 3. stopień toksyczności dotyczył zaledwie 5% z nich (nie zaobserwowano powikłań 4. stopnia). Grupę chorych, w której CAPOX zastosowano jako I linię leczenia, uznano za reprezentatywną i poddano ocenie skuteczność terapii w zależności od umiejscowienia guza pierwotnego.  Wnioski. Zaobserwowano różnice w przeżyciu całkowitym chorych po stratyfikacji względem lokalizacji guza pierwotnego. Przeżycie było dłuższe w przypadku lokalizacji guza pierwotnego po stronie lewej w porównaniu z umiejscowieniem prawostronnym i wynosiło — odpowiednio — 20,4 (95% CI 17,5–23,4) wobec 12,1 (95% CI 10,5–13,8) miesiąca (p = 0,014)

Ocena skuteczności chemioterapii z zastosowaniem kapecytabiny i oksaliplatyny u chorych na uogólnionego raka jelita grubego. Wpływ lokalizacji ogniska pierwotnego raka na skuteczność leczenia.

Introduction. Colorectal cancer is an increasingly common cancer, and due to the possibility of using many drugs nd combination therapy, it bears the hallmarks of a chronic disease. Improving the quality of life is important.  Material and methods. The following analysis applies to the oxaliplatin and capecitabine (CAPOX) regimen in a group of 305 patients. This chemotherapy was used as part of palliative treatment lines I, II or III.  Results. The work proved the effectiveness of the scheme despite the reduction of drug doses in about 50% of patients, and toxicity grade 3 was only present in 5% (grade 4 complications were not observed). The group of patients in which CAPOX was used as the first treatment line was considered representative, and the effectiveness of the treatment depending on the location of the primary tumour was evaluated.  Conclusion. Differences in overall survival of patients after stratification were observed relative to the location of the primary tumour. Survival was longer in patients with left-sided primary tumour compared to right-sided localisation and was, respectively, 20.4 (95% CI, 17.5–23.4) and 12.1 months (95% CI, 10.5–13.8) (P = 0.014).Rak jelita grubego jest coraz częstszym nowotworem, a dzięki możliwości stosowania wielu leków oraz terapii skojarzonej nosi znamiona choroby przewlekłej. Poprawa jakości życia ma istotne znaczenie. Poniższa analiza dotyczy schematu opartego o oksaliplatynę i kapecytabinę (CAPOX) w grupie 305 chorych. Chemioterapię tę zastosowano w ramach I, II lub III linii leczenia paliatywnego. W pracy udowodniono skuteczność schematu mimo redukcji dawek leków u około 50% chorych, a 3. stopień toksyczności dotyczył zaledwie 5% (powikłań 4. stopnia nie obserwowano). Grupę chorych, w której zastosowano CAPOX jako I linię leczenia, uznano za reprezentatywną i poddano ocenie skuteczność leczenia w zależności od umiejscowienia guza pierwotnego. Zaobserwowano różnice w przeżyciu całkowitym chorych po stratyfikacji względem lokalizacji guza pierwotnego. Przeżycie było dłuższe u chorych z guzem pierwotnym po stronie prawej w porównaniu z umiejscowieniem lewostronnym i wynosiło – odpowiednio – 20,4 (95% CI, 17,5-23,4) wobec 12,1 (95% CI, 10,5-13,8) miesiąca (p=0,014)

Common pathway signature in lung and liver fibrosis

<p>Fibrosis, a progressive accumulation of extracellular matrix components, encompasses a wide spectrum of distinct organs, and accounts for an increasing burden of morbidity and mortality worldwide. Despite the tremendous clinical impact, the mechanisms governing the fibrotic process are not yet understood, and to date, no clinically reliable therapies for fibrosis have been discovered. Here we applied Regeneration Intelligence, a new bioinformatics software suite for qualitative analysis of intracellular signaling pathway activation using transcriptomic data, to assess a network of molecular signaling in lung and liver fibrosis. In both tissues, our analysis detected major conserved signaling pathways strongly associated with fibrosis, suggesting that some of the pathways identified by our algorithm but not yet wet-lab validated as fibrogenesis related, may be attractive targets for future research. While the majority of significantly disrupted pathways were specific to histologically distinct organs, several pathways have been concurrently activated or downregulated among the hepatic and pulmonary fibrosis samples, providing new evidence of evolutionary conserved pathways that may be relevant as possible therapeutic targets. While future confirmatory studies are warranted to validate these observations, our platform proposes a promising new approach for detecting fibrosis-promoting pathways and tailoring the right therapy to prevent fibrogenesis.</p

Abstract PD11-09: PD11-09 Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study

Abstract Background: Patients with a/mTNBC have limited treatment options and a poor prognosis (objective response rate [ORR] of 37%, median duration of response 6.5 months, median overall survival 15.5 months for 1L chemotherapy [Rugo, et al. Ann Oncol. 2021 LBA16]). Combining checkpoint inhibitors with 1L chemotherapy modestly improves outcomes but only in PD-L1–positive a/mTNBC, emphasizing a critical unmet need for patients with PD-L1–negative disease and for further improving outcomes in PD-L1–positive disease. BEGONIA (NCT03742102) is an ongoing 2-part, open-label platform study, evaluating safety and efficacy of D, an anti–PD-L1 antibody, combined with other novel therapies in 1L a/mTNBC, including Dato-DXd, an antibody-drug conjugate consisting of a humanized anti-TROP2 antibody covalently linked to a highly potent topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. Early data from BEGONIA of D in combination with Dato-DXd showed promising responses. Here, we report updated results of Dato-DXd + D. Methods: Patients with unresectable a/mTNBC eligible for 1L treatment were enrolled, regardless of PD-L1 or TROP2 status, and received intravenous Dato-DXd 6 mg/kg + D 1120 mg every 3 weeks until progression or unacceptable toxicity. PD-L1, assessed using the VENTANA PD-L1 (SP263) Assay, was defined as high if ≥ 5% of the tumor area was populated by PD-L1–expressing tumor or immune cells. Primary endpoints were safety and tolerability. Secondary endpoints included investigator-assessed ORR (RECIST v1.1) and duration of response. Patients included in the efficacy analysis had ≥ 2 on-treatment disease assessments, progressed, died, or withdrew from the study. Results: As of April 8, 2022, 47 patients received Dato-DXd + D (39 ongoing) and 33 of those were included in the efficacy analysis. Median (range) follow-up was 7.5 (0–11) months. Patient age was a median of 51 years, 57% received prior treatment for early stage TNBC, and 60% had visceral metastases at baseline. Confirmed ORR was 26/33 (79%; 95% CI, 61–91); 2/33 patients (6%) had a complete response and 24/33 (73%) had a partial response. Confirmed response was irrespective of PD-L1 expression (PD-L1 high ORR, 4/5 [80%]; PD-L1 low, 16/21 [76%]; PD-L1 missing, 6/7 [86%] patients). Median duration of response was not reached; 100% of patients with a complete or partial response remained in response at 6 month follow-up, and 96% had an ongoing response at data cutoff. Adverse events (AEs) were manageable and consistent with the known safety profiles of each agent, with treatment-related AEs occurring in 41 patients (87%), any Grade 3/4 AEs in 17 patients (36%), and any serious AEs in 7 patients (15%). The most common all-Grade AEs were gastrointestinal (nausea in 26 patients [55%] and stomatitis in 24 patients [51%]). A low rate of diarrhea was reported (6 patients [13%], all Grade 1 or 2); 4 patients had anemia and 1 had neutropenia. There were no cases of interstitial lung disease/pneumonitis or thrombocytopenia. Nine patients (19%) and 11 patients (23%) underwent Dato-DXd dose reduction and delay, respectively; 14 (30%) had D dose delay. Treatment was discontinued due to an AE for 3 patients (6%). There were no deaths due to treatment-related AEs. Conclusions: In this updated analysis with additional patients and longer follow-up, the combination of Dato-DXd + D in 1L a/mTNBC demonstrated a manageable safety profile and compelling high response rates with promising durability. Although subgroups were small, responses occurred irrespective of PD-L1 expression. Further investigation of this treatment combination is warranted. Analysis of translational data is ongoing. Funding: AstraZeneca/Daiichi Sankyo Citation Format: Peter Schmid, Piotr Wysocki, Cynthia Ma, Yeon H. Park, Ricardo Fernandes, Simon Lord, Richard D. Baird, Catherine Prady, Kyung Hae Jung, Jamil Asselah, Robert Huisden, Ross Stewart, Petra Vuković, Ana T. Nunes, Zbigniew Nowecki. PD11-09 Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-09.</jats:p