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Postpartum depression and sexual dysfunction: a literature review
No full textPostpartum depression (PPD) and sexual dysfunction during the postpartum period frequently co-occur,sharing common neurobiological and hormonal mechanisms. This literature review synthesizes clinical,experimental, and systematic data on the pathomechanisms of PPD and associated sexual dysfunctions,with a particular focus on their clinical implications.A systematic search of PubMed, Embase, and Web of Science (1984–2025) identified 42 studies evaluatingneurosteroid levels (especially allopregnanolone), fluctuations in gonadal hormones, hypothalamic–pituitary–adrenal (HPA) axis dysfunction, GABA-A receptor function, neurotrophins (e.g., BDNF), inflammatorymarkers, and assessments of sexual function and maternal behaviors.The findings indicate that abrupt postpartum declines in allopregnanolone and gonadal hormones, HPAaxis dysregulation, and GABA-A receptor dysfunction contribute to low mood, anhedonia, and deficitsin sexual functioning, including reduced libido and difficulties with arousal. Alterations in neurotrophinsand proinflammatory cytokines exacerbate depressive and sexual symptoms, while psychosocial factorssuch as stress, maternal burdens, and a family history of depression further modulate the risk of dysfunction.Experimental and neuroimaging studies confirm the impact of these mechanisms on brain regionsresponsible for reward, motivation, and emotion regulation.The integration of neurobiological, hormonal, and psychosocial factors forms a comprehensive model ofPPD and sexual dysfunction as part of a shared continuum. Clinical implications include the need for earlyassessment of sexual function as a marker of PPD risk and the implementation of therapies addressing bothmood and sexual quality of life, such as neurosteroid-based treatments.Future research should employ longitudinal approaches, integrating neurobiological, hormonal, and psychosocialbiomarkers, to develop personalized therapeutic strategies for postpartum women
Latest advances in oral hormonal male contraception: efficacy, mechanisms of action, and future perspectives
No full textBetween 2008 and 2011, the rate of unintended pregnancies decreased by approximately 18% in the USA, largely due to the wider use of effective, long-acting, reversible contraceptives among women, such as intrauterine devices and subdermal implants. Despite advances in female contraception, the development of safe and convenient male contraceptive methods remains a significant clinical challenge. Current clinical research focuses on two oral hormonal agents: dimethandrolone undecanoate (DMAU) and 11β-methylnortestosterone dodecylcarbonate (11β-MNTDC). These synthetic androgenic and progestagenic steroids inhibit gonadotropin secretion and spermatogenesis by suppressing key molecules of the hypothalamic–pituitary–gonadal axis. Phase I and IIa trials have shown that they effectively suppress luteinizing hormone, follicle-stimulating hormone, and testosterone to contraceptive levels and have favorable safety profiles and mild adverse effects (e.g., slight weight gain and minor libido changes), with 11β-MNTDC associated with relatively milder adverse effects. DMAU and 11β-MNTDC differ slightly in their metabolic effects and tolerability. Longer-term phase IIb and III clinical trials are required to confirm their efficacy, reversibility, and safety. Both agents have the potential to become the first reversible oral hormonal male contraceptive.Between 2008 and 2011, the rate of unintended pregnancies decreased by approximately 18% in the USA, largely due to the wider use of effective, long-acting, reversible contraceptives among women, such as intrauterine devices and subdermal implants. Despite advances in female contraception, the development of safe and convenient male contraceptive methods remains a significant clinical challenge. Current clinical research focuses on two oral hormonal agents: dimethandrolone undecanoate (DMAU) and 11β-methylnortestosterone dodecylcarbonate (11β-MNTDC). These synthetic androgenic and progestagenic steroids inhibit gonadotropin secretion and spermatogenesis by suppressing key molecules of the hypothalamic–pituitary–gonadal axis. Phase I and IIa trials have shown that they effectively suppress luteinizing hormone, follicle-stimulating hormone, and testosterone to contraceptive levels and have favorable safety profiles and mild adverse effects (e.g., slight weight gain and minor libido changes), with 11β-MNTDC associated with relatively milder adverse effects. DMAU and 11β-MNTDC differ slightly in their metabolic effects and tolerability. Longer-term phase IIb and III clinical trials are required to confirm their efficacy, reversibility, and safety. Both agents have the potential to become the first reversible oral hormonal male contraceptive
Multicenter study of patients with transthyretin cardiac amyloidosis in Poland: Clinical characteristics, genotyping, electrocardiographic features, outcome predictors, and tafamidis treatment outcomes
No full textBackground: We present the first multicenter, non-interventional, longitudinal observational study of patients diagnosed with cardiac transthyretin amyloidosis (ATTR-CA) in Poland.Aims: The aim of this study was to describe the clinical characteristics, survival rates, and treatment outcomes of patients with ATTR-CA in Poland, and to identify potential markers linked to an increased risk of disease progression.Methods: Between 2017 and 2025, consecutive patients with confirmed ATTR-CA were evaluated at 4 cardiology centers. Assessments included blood tests, standard 12-lead electrocardiography, and transthoracic echocardiography. The primary endpoint was defined as death or heart transplantation.Results: ATTR-CA was confirmed in 115 patients, including 21 (18.2%) with hereditary disease. The median follow-up was 24 (12–41) months for the entire cohort and 25 (14.2–46.7) months for surviving patients (n = 78). The primary endpoint occurred in 37 (32.2%) patients. In multivariable analysis, the ratio of the transmitral early peak velocity (E) estimated by pulsed wave Doppler over the early mitral annulus velocity (e’), body mass index, and levels of high-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide were independent predictors of the primary endpoint. Tafamidis was received by 81 (70.4%) patients and was associated with significantly lower risk of the primary endpoint (P = 0.005), stroke, or transient ischemic attack (P = 0.047), and a markedly longer median survival (84 months [95% confidence interval, 68–116] vs. 14 months [95% confidence interval, 7–36]; log-rank P <0.0001). In tafamidis-treated patients, N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T levels remained stable at 6 and 12 months of follow-up, in contrast to untreated patients, who showed an increase in these biomarkers.Conclusions: This study provides the first multicenter data on ATTR-CA in Poland. Our findings enhance understanding of the disease course and treatment effects, underline the importance of disease-modifying therapy in improving outcomes, provide valuable real-world data on tafamidis treatment, and indicate directions for further research
The impact of pre- and post-diuretic urine osmolarity and serum osmolarity on one-year outcomes in acute heart failure patients during early decongestion
No full textBackground: Osmolarity is a key indicator of the balance between water and osmotically active molecules. It plays a crucial role in the diuretic response among patients with congestion in acute heart failure (AHF), and therefore, it may provide clinically meaningful information. Aims: This study investigated the association between urine (pre- and post-diuretic) and serum osmolarity during early diuretic treatment and one-year outcomes in AHF patients. Methods: It was single-center, prospective, observational study that included AHF. The patients were recruited between March 2021 and November 2023 and underwent one-year follow-up. Serum and urine osmolarity and their contributors (sodium, urea, glucose) were measured before loop diuretic exposure and 3 hours after infusion start. The main endpoints included: 1) all-cause mortality and 2) all-cause unplanned rehospitalizations. Results: In a one-year follow-up, 59 (23%) patients died (26 [10%] during index hospitalization), and 95 (40%) were rehospitalized. Higher pre-diuretic urine osmolarity was independently associated with a lower probability for mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.93–0.98; P <0.01) and rehospitalization (HR, 0.98; 95% CI, 0.95–0.99; P = 0.03). Pre-diuretic urine osmolarity was significantly lower in patients with an event during follow-up (359 [272–403] vs. 419 [332–509] mOsm/l; P <0.001 for mortality and 384 [303–463] vs. 430 [342–524] mOsm/l; P = 0.03 for rehospitalization). Moreover, the degree of urine osmolarity drop was lower in patients who died (32 [8–77] vs. 122 [50–208] mOsm/l; P <0.001) and significantly influenced death probability (0.93 [0.89–0.97]; P <0.01), while significance was not proven regarding rehospitalizations (0.98 [0.95–1.00]; P = 0.16). Serum and post-diuretic urine osmolarity had no prognostic significance. Conclusions: Pre-diuretic urine osmolarity and the degree of its decrease (reflecting the potential for urine dilution) during early decongestion are associated with one-year outcomes in AHF
Enkorafenib z binimetynibem — skuteczność w pierwszej, drugiej i trzeciej linii leczenia chorych na zaawansowanego czerniaka z mutacją BRAF — badanie w warunkach rutynowej praktyki klinicznej
No full textIntroduction. In patients with advanced melanoma with BRAF mutation, the BRAF and MEK inhibitors can be used before or after immunotherapy, and even as third-line systemic treatment. To date, majority of available data on encorafenib plus binimetinib comes from clinical trials.
Material and methods. This was a multicenter retrospective study, which aimed to investigate the efficacy of encorafenib plus binimetinib (E+B) treatment in patients with unresectable stage III or IV melanoma in the real-world setting. The study did not include patients treated with adjuvant intent. Progression-free survival (PFS) and overall survival (OS) estimates were obtained using Kaplan–Meier method.
Results. There were 130 patients treated in the first-line setting. Their median follow-up was 24.1 (95% CI 20.9–32) months. Median age of the group treated with E+B first line treatment was 63.5 years and LDH level was abnormal in 53.1% of cases, while 25.4% of patients had brain metastases. The median PFS was 10.3 (95% CI 8–12.4) months, 1- and 3-year PFSs were 40.1% (95% CI 31.9–50.3) and 12.3% (95% CI 6.1–24.7), while the objective response rate (ORR) was 58.5%. After the progression of the disease, 32 (24.6%) patients received second-line treatment (including immunotherapy in 28, 87.5% cases) and 5 (3.8%) patients received third-line treatment. The median OS from the start of the first-line treatment was 15.8 (95% CI 12–23.5) months, while the 1-year and 3-year OS rates were 58% (95% CI 49.6–67.9) and 20% (95% CI 11.9–33.6), respectively. In the second-line treatment, after the anti-PD-1-based first-line treatment, the E+B was administered in 82 patients. The median PFS was 8.5 (95% CI 6.5–12) months, and the ORR was 42 (51.2%). The median OS from the start of the second-line treatment was 13.2 (95% CI 10.9–22) months. In the third-line treatment, E+B was used in 23 patients, with 6- and 12-month PFS being 23% (95% CI 10.7–49.6), and 13.8% (95% CI 4.8–39.4), respectively. The median PFS in third-line setting was 3.6 (95% CI 2.8–5.3) months.
Conclusions. This real-world evidence supports the clinically meaningful efficacy of the combination of E+B in first-, second- and third-line treatment.Wprowadzenie. U chorych na zaawansowanego czerniaka z mutacją BRAF, inhibitory BRAF i MEK mogą być wykorzystywane przed lub po immunoterapii, a także jako leczenie systemowe trzeciej linii. Dotychczas większość danych dotyczących enkorafenibu z binimetynibem pochodzi z badań klinicznych.
Materiał i metody. Przeprowadzono wieloośrodkowe badanie retrospektywne, którego celem była ocena skuteczności enkorafenibu z binimetynibem (E+B) u chorych na zaawansowanego czerniaka w III (nieresekcyjny) lub IV stopniu zaawansowania w warunkach rutynowej praktyki klinicznej. Nie włączono do analizy pacjentów leczonych uzupełniająco. Czas przeżycia do progresji (PFS, progression-free survival) i czas przeżycia całkowitego (OS, overall survival) oceniono z wykorzystaniem estymatora Kaplana–Meiera.
Wyniki. W pierwszej linii było leczonych 130 chorych. Mediana czasu obserwacji wyniosła 24,1 miesiąca (95% CI 20,9–32). Mediana wieku w tej grupie to 63,5 lat, natomiast 53,1% chorych miało wyjściowo podwyższony poziom LDH, a 25,4% przerzuty w ośrodkowym układzie nerwowym (OUN). Mediana PFS wynosiła 10,3 miesiąca (95% CI 8–12,4), 1- i 3-letni odsetek PFS wyniósł odpowiednio 40,1% (95% CI 31,9–50,3) i 12,3% (95% CI 6,1–24,7), a odsetek obiektywnych odpowiedzi (ORR, objective response rate) 58,5%. Po progresji choroby 32 (24,6%) chorych otrzymało leczenie drugiej linii (w tym 28 immunoterapię, 87,5% przypadków), a 5 (3,8%) chorych otrzymało leczenie trzeciej linii. Mediana OS od rozpoczęcia leczenia pierwszej linii wyniosła 15,8 miesiąca (95% CI 12–23,5), podczas gdy odsetki OS po 1 roku i 3 latach wyniosły odpowiednio 58% (95% CI 49,6–67,9) i 20% (95% CI 11,9–33,6). W leczeniu drugiej linii, po leczeniu pierwszej linii przeciwciałami anty-PD-1, E+B podano 82 chorym. Mediana PFS wyniosła 8,5 miesiąca (95% CI 6,5–12), a ORR wyniósł 42 (51,2%). Mediana OS od początku leczenia drugiej linii wyniosła 13,2 miesiąca (95% CI 10,9–22). W leczeniu trzeciej linii schemat E+B zastosowano u 23 chorych, a 6- i 12-miesięczne odsetki PFS wyniosły odpowiednio 23% (95% CI 10,7–49,6) i 13,8% (95% CI 4,8–39,4). Mediana PFS w trzeciej linii leczenia wyniosła 3,6 miesiąca (95% CI 2,8–5,3).
Wnioski. Te dowody z praktyki klinicznej potwierdzają klinicznie istotną skuteczność połączenia E+B w leczeniu pierwszej, drugiej i trzeciej linii
Melatonin as a modulator of skin barrier
No full textBackground: Melatonin, beyond its role in circadian rhythm regulation, exhibits antioxidant, anti-inflammatory, immunomodulatory, and anti-apoptotic properties. Recent studies suggest that it supports skin barrier integrity by modulating oxidative stress, inflammation, and lipid homeostasis, offering therapeutic potential in conditions such as atopic dermatitis (AD) and photoaging.
Methods: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and Web of Science were searched for studies published between January 1993 and March 2025 using the keywords “melatonin,” “oxidative stress,” and “skin barrier.” Both experimental and clinical studies were included. After screening 502 records and removing duplicates, 35 articles met the eligibility criteria. Extracted data covered molecular mechanisms, biological effects, and clinical outcomes related to skin barrier function.
Results: Mechanistic evidence indicates that melatonin enhances epidermal integrity by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway, inhibiting nuclear factor kappa B (NF-κB) signaling, and upregulating tight junction proteins. In experimental models, topical and systemic administration improved hydration, elasticity, and protection against ultraviolet (UV)-induced damage whereas clinical data, though limited, suggest potential benefits in photoprotection. Melatonin also modulates the circadian–microbiota axis and mitochondrial activity, contributing to skin regeneration and homeostasis.
Conclusions: Melatonin acts as a multifunctional regulator of skin barrier mechanisms in preclinical settings. It represents a promising candidate for supportive therapy, though robust clinical trials are required to confirm its efficacy in dermatological practice
Safe reinitiation of ruxolitinib therapy in a patient with polycythemia vera and multiple comorbidities after a treatment interruption due to pulmonary tuberculosis hospitalization
No full textWprowadzenie: Wielochorobowość stanowi istotne obciążenie zdrowotne, którego częstość wzrasta wraz z wiekiem. Lekarz prowadzący pacjenta musi uwzględniać potencjalny wpływ terapii na choroby współistniejące. Oprócz typowych działań niepożądanych stosowanego leczenia należy brać pod uwagę możliwość interakcji lekowych wynikających z polipragmazji.
Opis przypadku: W opisanym przypadku przedstawiono historię chorej na czerwienicę prawdziwą, u której po 12 latach skutecznej terapii hydroksymocznikiem rozwinęły się objawy nietolerancji. Kolejne linie leczenia wiązały się z występowaniem powikłań. Pomimo skomplikowanej historii chorobowej oraz koniecznej dłuższej przerwy w terapii, udało się bezpiecznie wznowić leczenie ruksolitynibem.
Wnioski: Terapia ruksolitynibem nie nasiliła objawów chorób współistniejących, nie wymagała modyfikacji wcześniej stosowanych leków, zmniejszyła ryzyko zdarzeń zakrzepowo-zatorowych oraz korzystnie wpłynęła na proces powrotu pacjentki do pełnej sprawności fizycznej.Introduction: Multimorbidity is a significant health burden prevelance of which increases with age. Clinicians managing an additional disease must consider the potential impact of their therapy on coexisting conditions. In addition to the typical adverse effects of prescribed treatments, the possibility of drug–drug interactions related to necessary polypharmacy should also be taken into account.
Case report: The case described presents the history of a patient with polycythemia vera who, after 12 years of effective hydroxyurea therapy, developed symptoms of intolerance. Subsequent lines of treatment were complicated by further adverse events. Nevertheless, despite a complex medical history and a prolonged necessary treatment interruption, ruxolitinib therapy was safely resumed.
Conclusions: Ruxolitinib did not exacerbate comorbid conditions, did not require modification of previously prescribed therapies, reduced the risk of thromboembolic events, and contributed to the patient’s return to full physical function
Choroba gęstych złogów związana z przeciwciałami przeciwko błonie podstawnej kłębuszków nerkowych — opis przypadku
No full textGlomerulopatia C3 jest rzadkim typem kłębuszkowego zapalenia nerek, którego roczną częstość występowania szacuje się na 1–2 przypadki na milion osób. Rozróżnienie dwóch głównych podtypów glomerulopatii C3: choroby gęstych złogów i kłębuszkowego zapalenia nerek C3 wymagają zastosowania mikroskopii elektronowej. Głównym objawem glomerulopatii C3 jest białkomocz, któremu zwykle towarzyszy krwiomocz; nasilenie obu objawów zależy od rodzaju i intensywności uszkodzenia kłębuszków. Przedstawiamy przypadek pacjenta z chorobą gęstych złogów (DDD, dense deposit disease) cierpiącego na błoniasto-rozplemowe kłębuszkowe zapalenie nerek (MPGN, membranoproliferative glomerulonephritis) typu 1 rozpoznane w 2010 roku i nowym początkiem zespołu nerczycowego związanego z przeciwciałami przeciwko błonie podstawnej kłębuszków nerkowych
Postępy w leczeniu nefropatii immunoglobuliny A
No full textW artykule omówiono zalecenia Kidney Disease: Improving Global Outcomes (KDIGO) 2025 dotyczące postepowania w nefropatii immunoglobuliny A (IgA, immunoglobulin A). Według ekspertów należy jednocześnie wdrażać terapie hamujące powstawanie galaktozodeficientnej (Gd, galactose-deficient) IgA1 i kompleksów immunologicznych (IgA-IC, IgA immune complexes) oraz spowalniające proces zapalny w kłębuszku, a także łagodzić progresję przewlekłej choroby nerek (PChN). W artykule omówiono zastosowanie budezonidu o zmodyfikowanym uwalnianiu, glikokortykosteroidów systemowych oraz leków wpływających na funkcję limfocytów B [hamujących czynnik aktywujący limfocyty B (BAFF, B-cell activating factor) i ligand A indukujący proliferację (APRIL, A proliferationinducing ligand)], a także rolę układu dopełniacza, hamowanie czynnika B i inhibitory receptora endoteliny. Uwzględniono wyniki ostatnich badań klinicznych i rejestracje nowych leków
Fusion variants of the ALK gene — the key to modern therapy for patients with ALK-positive non-small-cell lung cancer
Full text linkSince the discovery of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion in non-small-cell lung cancer (NSCLC), followed by the identification of many different fusion variants, molecularly targeted therapy has revolutionized treatment for patients with ALK-positive lung cancer. Recent research has focused on understanding how specific variants may influence the biological and molecular behavior of cancer cells and how this knowledge can be used in routine clinical practice. This article explores the current understanding of EML4-ALK variants and highlights unanswered questions in the field