BACKGROUND: In patients with steroid-resistant nephrotic syndrome (SRNS), the presence of monogenic variants influences therapeutic strategies. Large cohort studies reported the detection of monogenic variants in approximately 30% of patients with SRNS. However, these cohorts included many patients, such as those with symptomatic proteinuria, who did not meet the strict diagnostic criteria for pediatric nephrotic syndrome (NS). Therefore, we investigated the proportion of causative monogenic variants detected in patients who strictly met the diagnostic criteria of SRNS and explored their clinical characteristics.
METHODS: We examined pediatric SRNS cases with genetic analysis conducted in our hospital. Cases satisfying all of the following criteria were included: (1) age at onset 1-18 years, (2) serum albumin at onset ≤ 2.5 g/dl, (3) persistent heavy proteinuria, and (4) no complete remission after 4 weeks of steroid monotherapy.
RESULTS: The proportion of detected monogenic variants was 12% (22/185) among all patients. The proportion was only 7% (9/129) in patients with edema at disease onset compared with 38% (9/24) in those without (p < 0.0001). Monogenic variants were rare in patients with acute kidney injury associated with NS (1% (1/11)) or a history of complete remission (4% (2/51)).
CONCLUSIONS: Our study revealed a monogenic cause in 12% of individuals with strictly defined SRNS, a much smaller proportion than previously reported. The presence or absence of edema at the onset was an important factor to distinguish SRNS with monogenic cause from SRNS without. Our results provide further evidence of the SRNS types attributable to monogenic causes.

In the field of severe asthma, the concept of disease control has recently been integrated by the one of clinical remission. With this new concept, we move on to analyze the efficacy of therapy on multiple parameters simultaneously, starting with the mandatory discontinuation of the systemic glucocorticoids, to which is added the effect on exacerbations, respiratory function, and symptoms control. The Italian severe asthma registry SANI (Severe Asthma Network Italy) drafted criteria for the definition of disease remission, allowing patients to be classified into two groups, partial and complete remission. The greater dynamism of the definition, provided by SANI, allows us to hypothesize its practical use, concerning therapy management of severe asthma patients, starting from the level of remission, with the aim to facilitate the clinical decision on replacement, continuation or modulation of patients\' therapy.

Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997-2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; n = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; P = .014) and showed an odds ratio of 0.26 for CR (P = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10-0.60; P = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and -0.13/-0.15, respectively; P < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.

To date, few cases of concurrent acute myeloid leukemia (AML) and untreated chronic lymphocytic leukemia (CLL) have been reported. Due to the complexity of the pathogenesis and the absence of a uniform treatment regimen, the associated prognosis remains poor. The present study reports the case of a 58-year-old male with asymptomatic leukocytosis, who was previously healthy with no malignancies. Flow cytometry analysis revealed protocytosis, monocytosis and monoclonal B lymphocytosis in a bone marrow specimen. Results of a gene rearrangement assay demonstrated positive immunoglobulin heavy-chain variable region gene status in monoclonal B lymphocytes. Thus, the patient was diagnosed with AML with maturation (AML-M2) that co-existed with untreated CLL. The normative daunorubicin (40 mg/m2 on days 1-3) and cytarabine (80 mg/m2 on days 1-7) regimen combined with venetoclax (400 mg on days 1-7) and rituximab (375 mg/m2 on day 0) was used as induction chemotherapy. The patient achieved morphological complete remission in both AML and CLL following the first course of chemotherapy. In addition, the present study retrospectively analyzed the data of 22 patients with concurrent AML and untreated CLL, and the results demonstrated that the median age at the time of AML diagnosis was 69 years (range, 52-86 years). Moreover, the male:female ratio was 6.33:1 and AML-M2 was the most frequent subtype at diagnosis. The presence of a complex karyotype was associated with the poorest prognosis, and patients who received venetoclax often exhibited an improved prognosis. In conclusion, the combination of venetoclax and rituximab improves the prognosis of patients with concurrent AML and untreated CLL.

OBJECTIVE: Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms.
METHODS: Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms.
RESULTS: 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up.
CONCLUSIONS: In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission.

BACKGROUND: In its severe form, where possible, asthma is treated using biological drugs in order to reduce, as much as possible, the use of systemic steroids. Mepolizumab is effective for severe asthma based on key outcomes such as exacerbation and steroid dependence. Its efficacy in terms of the criteria for clinical remission in the short and long term has become of interest.
OBJECTIVE: We aimed to evaluate the effect of mepolizumab in the achievement of clinical remission after 3 years of administration.
METHODS: In this study, 71 patients who continued mepolizumab for 3 years were assessed for clinical remission according to six different published sets of remission criteria.
RESULTS: According to the criteria, 39-52% of patients experienced complete remission in the first year, increasing to 51-73% at 3 years. By classifying patients according to partial and complete remission criteria, proposed by the SANI, we observe 22% of patients in partial remission at one year, achieving complete remission after three years. The baseline factors associated with earlier remission were a higher FEV1, if we consider classifications requiring an FEV1 ≥ 80%, a low OCS dose, and low FeNO levels, in the patients requiring FEV1 stabilization.
CONCLUSIONS: Clinical remission is possible for patients treated with mepolizumab. The observations at three years compared with the first year indicated that the factors negatively affecting remission delayed rather than prevented it. Earlier treatment could increase the chances of remission.

Bullous pemphigoid (BP) is a rare blistering disease often considered a primary sign of a paraneoplastic syndrome. Retrospective studies have established its link with hematological malignancies, particularly lymphoproliferative disorders. Here, we present what we believe to be the inaugural case of successful simultaneous management of BP and de novo acute myeloid leukemia (AML) in a 28-year-old male patient. Given the rarity and severity of both conditions, our treatment strategy aimed to maximize efficacy by combining immunosuppressive therapy (initially plasmapheresis with high-dose corticosteroids, followed by anti-CD20 monoclonal antibody and intravenous immunoglobulins 2 g/m2) with lymphodepleting antileukemic chemotherapy utilizing Fludarabine (FLAG-IDA induction regimen). Following diagnosis, considering the patient\'s youth and the concurrent presence of two rare and potentially life-threatening diseases, we opted for an aggressive treatment. Upon achieving complete morphological remission of AML with measurable residual disease (MRD) negativity, despite incomplete resolution of BP, we proceeded with high-dose cytarabine consolidation followed by peripheral stem cell harvest and autologous stem cell transplantation (ASCT). Our conditioning regimen for ASCT involved Bu-Cy with the addition of anti-thymocyte globulins. At day + 100 post-ASCT, bone marrow evaluation confirmed morphological remission and MRD negativity. Meanwhile, BP had completely resolved with normalization of BP180 antibody levels.

UNASSIGNED: The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen.
UNASSIGNED: We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively.
UNASSIGNED: Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (P < 0.001). At the same time, the VEN-HMA group exhibited a significant survival advantage compared to the HAG treatment group(HR = 0.328, 95%CI: 0.158-0.683, P = 0.003).In patients with relapsed and refractory acute myeloid leukaemia, 43.8% of patients in the VEN-HMA treatment group achieved complete remission, which was similar to the 50% in the HAG treatment group (P > 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (P = 0.290).
UNASSIGNED: In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted.

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient\'s complete remission has persisted for 20 months after HSCT.

We report a rare case of an extremely old colorectal cancer (CRC) patient who had complete remission after liver metastasectomy and stereotactic body radiotherapy (SBRT) to lung oligometastases (OM), with good quality of life and no evidence of recurrence 12 years after the initial diagnosis. An 83-year-old male patient had a right hemicolectomy for stage pT3 pN0 adenocarcinoma of the colon. Soon he was found to have liver metastasis treated with radiofrequency ablation and then liver metastasectomy with clear margins, followed by chemotherapy in the form of FOLFIRI for six months. Six years later, positron emission tomography (PET) showed 1.6 cm OM in the left upper lobe lung. He was not considered a good candidate for surgery. We offered him SBRT 48 Gy in four fractions every other day. The lesion disappeared with no recurrence in the same location on PET and serial computed tomography (CT) scans. Three years later, PET-CT found a new OM in the left lingular lung measuring 1.2 cm. A CT-guided lung biopsy confirmed invasive adenocarcinoma favoring OM from the CRC. SBRT planning failed due to its proximity to the heart. He accepted the longer course of conventional volumetric modulated arc therapy at 60 Gy in 15 fractions with daily cone-beam CT guidance. Again, he tolerated treatment very well with no significant side effects, despite his age. He did not require any chemotherapy or other systemic treatment in the last 11 years, so he did not experience any toxicities related to such treatment. This case is important to show that old age alone should not be considered a contraindication for metastasectomy and SBRT for CRC with liver and lung OM.