Complete Remission Of Disease Research Articles

A bispecific antibody targeting HLA-DQ2.5-gluten peptides potently blocks gluten-specific T cells induced by gluten ingestion in patients with celiac disease

The gluten-free diet for celiac disease (CeD) is restrictive and often fails to induce complete symptom and/or mucosal disease remission. Central to CeD pathogenesis is the gluten-specific CD4+ T cell that is restricted by HLA-DQ2.5 in over 85% of CeD patients, making HLA-DQ2.5 an attractive target for suppressing gluten-dependent immunity. Recently, a novel anti-HLA-DQ2.5 antibody that specifically recognizes the complexes of HLA-DQ2.5 and multiple gluten epitopes was developed (DONQ52). ObjectiveTo assess the ability of DONQ52 to inhibit CeD patient-derived T-cell responses to the most immunogenic gluten peptides that encompass immunodominant T cell epitopes. MethodsWe employed an in vivo gluten challenge model in patients with CeD that affords a quantitative readout of disease-relevant gluten-specific T-cell responses. HLA-DQ2.5+ CeD patients consumed food containing wheat, barley, or rye for 3 days with collection of blood before (D1) and 6 days after (D6) commencing the challenge. Peripheral blood mononuclear cells were isolated and assessed in an interferon (IFN)-γ enzyme-linked immunosorbent spot assay (ELISpot) testing responses to gluten peptides encompassing a series of immunodominant T cell epitopes. The inhibitory effect of DONQ52 (4 or 40 μg/mL) was assessed and compared to pan-HLA-DQ blockade (SPVL3 antibody). ResultsIn HLA-DQ2.5+ CeD patients, DONQ52 reduced T cell responses to all wheat gluten peptides to an equivalent or more effective degree than pan-HLA-DQ antibody blockade. It reduced T cell responses to a cocktail of the most immunodominant wheat epitopes by a median of 87% (IQR 72–92). Notably, DONQ52 also substantially reduced T-cell responses to dominant barley hordein and rye secalin derived peptides. DONQ52 had no effect on T-cell responses to non-gluten antigens. ConclusionDONQ52 can significantly block HLA-DQ2.5-restricted T cell responses to the most highly immunogenic gluten peptides in CeD. Our findings support in vitro data that DONQ52 displays selectivity and broad cross-reactivity against multiple gluten peptide:HLA-DQ2.5 complexes. This work provides proof-of-concept multi-specific antibody blockade has the potential to meaningfully inhibit pathogenic gluten-specific T-cell responses in CeD and supports ongoing therapeutic development.

Efficacy and Safety of Dupilumab in the Treatment of Hand Eczema: A Retrospective Study.

Background: Hand eczema (HE) is a prevalent chronic condition that exerts a substantial and enduring adverse effect on quality of life (QoL) and imposes an economic burden on society. Managing HE poses challenges due to the limited effectiveness and potential adverse effects associated with many currently available topical and systemic treatments. Methods: This article examines twenty-one patients affected by HE treated with dupilumab, a fully human monoclonal antibody targeting interleukin IL-4 and IL-13 signaling. This involves a retrospective descriptive statistical analysis. Results: At week 6, HECSI-75 was achieved by 12 patients (57.9%). The proportion of patients meeting the HECSI-75 criteria steadily increased over the observation weeks, reaching 90% at week 16 and 100% at week 104. Furthermore, HECSI-90 and HECSI-100 were achieved by 75% and 60% of patients at week 16 and by 100% and 85% of patients at week 68, respectively. All patients who reached week 104 maintained complete disease remission according to HECSI 100. Conclusions: In all patients, dupilumab was shown to be an effective drug in achieving disease clearance, as indicated by all the parameters considered at each evaluation point (Week 6, Week 16, Week 32, Week 52, Week 68, Week 84, and Week 104), in comparison to the initial baseline.

Complete remission of perineal extra-mammary Paget's disease by curative-intent radiotherapy using volumetric modulated arc therapy in a patient older than 90 years.

Localized extra-mammary Paget's disease (EMPD) is mainly treated with surgical resection. Curative radiation therapy (CRT) is an alternative to surgery. Electron beams and conventional X-ray methods have been used in patients with EMPD for radiotherapy. The present report describes the case of a very elderly patient with perineal EMPD who was treated with definitive radiotherapy consisting of 60 Gy in 30 fractions. Surgery was deemed too difficult because of his age and comorbidities. We adopted volumetric modulated arc therapy as the radiotherapy modality, a recent, advanced form of intensity-modulated radiation therapy. Grade 3 dermatitis was observed as an acute phase adverse event, and he achieved a complete response and maintained remission for over one-year post-treatment. Our radiotherapy treatment protocol resulted in good clinical outcomes; therefore, it may be a candidate for inoperable patients with EMPD.

Normal Infant Immunologic Assessment and Uneventful Live Rotavirus Vaccination Despite Continuous Tofacitinib Exposure In Utero and During Breastfeeding.

Janus kinase (JAK) inhibitors are effective for the treatment of inflammatory bowel disease (IBD). However, this class of medications is not recommended during pregnancy or breastfeeding based on animal data suggesting teratogenesis and recent reports of transmammary transfer after maternal ingestion, raising concerns for immune system development in babies exposed to these drugs. We present the case of a patient with IBD treated with a JAK inhibitor who decided to continue the medication throughout her pregnancy and during breastfeeding. This is the first reported case of a detailed immunologic profile in a baby exposed to tofacitinib in utero and during lactation. A 30-year-old female with ulcerative colitis with previous exposure to vedolizumab and infliximab achieved complete remission with tofacitinib therapy. The patient became pregnant after 5 months of JAK inhibitor therapy and decided to continue tofacitinib during pregnancy and while breastfeeding. The patient delivered a healthy offspring with no congenital malformations, a normal detailed immunologic profile, and subsequent safe provision of the live oral rotavirus vaccine. This case highlights the importance of individualized counseling for patients of childbearing age who are candidates for JAK inhibition. Those who are pregnant or breastfeeding with refractory disease may have limited medical therapeutic options. Ongoing effective therapy for IBD resulted in complete disease remission in the mother and favorable outcomes in the infant. Further, an in-depth infant immunological assessment can lead to specific vaccination recommendations in exposed infants.

Demyelinating Polyradiculoneuropathy in Chronic Lymphocytic Leukemia: A Case Report on BTKis versus Venetoclax-Rituximab

The dysregulation of the immune system in Chronic Lymphocytic Leukemia (CLL) often allows for the development of immune-mediated diseases. Among them, autoimmune cytopenias are the most common, but cases of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been reported. We herein report on a patient who developed a CIDP while undergoing ibrutinib treatment for CLL, prompting drug discontinuation. Steroid treatment and a rituximab course proved to be ineffective at obtaining long-term control of CIDP, but therapy with venetoclax and rituximab, which was started due to CLL progression, led to the progressive amelioration of the symptoms up to complete remission of the neurological disease.

Safety and Efficacy of Autologous HSCT in Nine Patients with AIDS-Related Non-Hodgkin Lymphoma

Background：In recent years, with the application of HIV combined with resistance retroviral therapy, the number of AIDS-NHL patients has gradually increased, surpassing Kaposi's sarcoma and becoming the first AIDS-related tumor. The prognosis of AIDS-NHL patients is worse than that of ordinary NHL patients, and more powerful treatment is needed. To analyze the safety and efficacy of 9 AIDS-related non-Hodgkin lymphoma (AIDS-related non-Hodgkin lymphoma, AIDS-NHL) treated with autologous hematopoietic stem cell transplantation (auto-hematopoietic stem cell transplantation, ASCT). Methods: 9 patients with AIDS-NHL were prospectively treated for their safety and efficacy. Results: The male to female ratio of 9 AIDS-NHL patients was 8:1, and the median age was 38 years. The pathology types were 4 DLBCL, 2 PBL, 1 BL, 1 HGBL and 1 HL, including 3 patients with refractory relapse (1 each of DLBCL, HGBL and PBL). Except for three patients with refractory relapse, the remaining six patients underwent first-line autologous HSCT. One PBL stage was in stage I low-risk group and the remaining patients were in stage III - IV high-risk group. Before transplantation, one patient was progressive, one patient was in partial remission, and the other patients achieved complete remission after chemotherapy. All patients underwent autologous HSC mobilization using PEG-G-CSF, with all CD34 + cell numbers> 210 ^ 6 / Kg. Transplantation pretreatment was performed with the BeEAM protocol, with a median time to granulocyte engraftment of 11 days and a median time to platelet engraftment of 14 days, with no transplant-related death. Two patients who did not achieve CR before transplantation all died due to disease progression within 3 months after transplantation, and the remaining patients remained in complete disease remission through follow-up until February 28,2023. Conclusion: AIDS-NHL patients are aggressive and have a poor prognosis, and active treatment is needed to improve their long-term survival. Our center prospectively performed autologous HSCT in nine patients with AIDS-NHL, and the results showed that the time of granulocyte and platelet engraftment was consistent with that of ordinary NHL patients, with no transplant-related death and was well tolerated. Failure to achieve complete remission before transplantation may be one of the adverse factors for the early death of patients.

A multicenter real-world analysis of risk factors, therapeutics, and outcomes of patients with metastatic basal cell carcinoma

BackgroundMetastatic BCC (mBCC) is rare and there are limited data regarding patient and tumor risk factors, optimal treatments, and disease prognosis. ObjectiveTo assess patient and tumor characteristics, therapeutics, and outcomes of mBCC stratified by location of metastasis. MethodsRetrospective cohort study of fifty-three patients with mBCC treated at four large academic centers in Boston, Massachusetts; Philadelphia, Pennsylvania; and Cleveland, Ohio between January 1, 2005 to December 31, 2021. ResultsA total of 53 patients with mBCC were identified across 4 centers, 22 (42%) of whom had mBCC with spread limited to lymph nodes and 31 (58%) patients with distant organ spread (with or without lymph node involvement). Overall, half (n=11) of patients with nodal metastasis achieved complete remission of disease, compared to just 1 (3%) patient with distant metastasis. The 5-year survival for nodal and distant metastatic patients was 89.3% and 61.0%, respectively. LimitationsSmall sample size due to disease rarity Conclusions and RelevancePatients with nodal disease are more likely to have disease remission whereas patients with distant metastasis are more likely to have persistent disease and die from their disease. However, 5-year survival rates exceed 50%, even for stage IV disease.

Disease Awareness and Treatment Preferences in Vitiligo: A Cross-sectional Study in China.

In China, there is a lack of data regarding the awareness and treatment preferences among patients with vitiligo and their families. To address this gap, a cross-sectional questionnaire-based study was conducted to investigate disease awareness and treatment preferences in Chinese patients with vitiligo. The study also evaluated willingness to pay, using 2 standardized items, and assessed quality of life, using the Dermatology Life Quality Index (DLQI) score. Data from 307 patients with vitiligo (59.3% women, mean age 28.98 years, range 2-73 years) were analysed. Of these patients, 44.7% had insufficient knowledge of vitiligo, particularly those from rural areas or with low levels of education. Mean DLQI total score was 4.86 (5.24 for women and 4.30 for men). Among the most accepted treatments were topical drugs, phototherapy, and systemic therapy. Patients were relatively conservative about the duration and cost of treatment, with only 27.7% willing to pay more than 10,000 Chinese yuan renminbi (CNY) for complete disease remission. High level of education, high income, skin lesions in specific areas, and skin transplantation therapy predicted higher willingness to pay. Insufficient knowledge was associated with a higher burden of disease. In order to reduce the disease burden and improve treatment adherence it is crucial to enhance disease awareness and take into account patient preferences.

OA14 The role of anifrolumab in treating life threatening systemic lupus erythematosus with severe mucocutaneous involvement

OA14 The role of anifrolumab in treating life threatening systemic lupus erythematosus with severe mucocutaneous involvement

A Case Report and Literature Review of Primary Central Nervous System Lymphoma in a Patient with Crigler–Najjar Syndrome: How We Managed

AbstractPrimary central nervous system lymphoma (PCNSL) is a rare form of CNS tumor that can be managed with curative intent using high-dose chemotherapeutic drugs. High-dose methotrexate is an essential drug for the management of PCNSL. We present a case of a 26-year-old man with a known comorbidity of Crigler–Najjar syndrome type II and a baseline bilirubin of 13.5 mg/dL, presented with somnolence and ataxia. In view of hyperbilirubinemia, the optimal treatment for CNS lymphoma, the De Angelis protocol, was modified for this patient. The patient tolerated the chemotherapy well with manageable fluctuations in bilirubin levels, followed by consolidation with whole-brain radiotherapy. He remains asymptomatic 6 months after the onset of the symptoms with the disease in complete remission. We highlight here this unusual case of PCNSL where high-dose methotrexate was used with close observation of liver function in view of hyperbilirubinemia in a known case of Crigler–Najjar syndrome.

Experience with abatacept in refractory lupus nephritis.

Lupus nephritis is a major cause of morbidity in patients with systemic lupus erythematosus. Responsiveness to treatment is crucial to avoid chronic kidney disease. New molecules have been developed in recent years to improve renal survival rates. Biological therapies as coadjutant to conventional induction treatment have been tested in randomized clinical trials with heterogeneous results. Like many others biologic therapies, Abatacept has not shown a clear benefit in the context of clinical trials. We present two cases of lupus nephritis patients in whom addition of abatacept resulted in complete remission of the renal disease. The first case described a 49-year-old male with class IV lupus nephritis with nephrotic range proteinuria and high immunological activity refractory to conventional treatment with cyclophosphamide and corticosteroids and multitarget therapy with tacrolimus, mycophenolate mofetil and prednisone. Several biological therapies (rituximab, belimumab and tocilizumab) were unsuccessfully tried, so that abatacept was added to his background multitarget therapy showing complete clinical response. The second case described a 52-year-old female with class IV lupus nephritis treated initially with conventional treatment with partial response. In successive renal flares with nephrotic proteinuria, she showed intolerance to rituximab and refractoriness to voclosporin. Finally, abatacept was added to her background therapy with MMF and PDN showing complete and maintained remission of the disease. In no case the use of abatacept was associated with serious adverse events. Based on our experience, abatacept should be considered as a safe rescue therapy in patients with refractory lupus nephritis and proteinuria with nephrotic range. In addition to this case, we reviewed the use of abatacept in lupus nephritis in the literature.

Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma.

Refractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease. Between 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters. All patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome. Autologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial.

Predictors of complete remission of type 2 diabetes in patients over 65 years of age – a multicenter study

IntroductionThe type 2 diabetes (T2D) improvement rate in the elderly is high after bariatric and metabolic surgery, but not all patients achieve complete remission of disease. There are some predictors for T2D remission after bariatric surgery in patients of different ages, but there are few studies describing these factors in elderly patients. The study aimed to determine predictors for diabetes remission after bariatric surgery among patients over 65 years of age.Material and methodsA retrospective study analyzed patients over 65 years with T2D who underwent laparoscopic bariatric procedures in European country from 2008 to 2022. Multivariate logistic regression analysis was performed to obtain significant, independent risk factors.ResultsThe group consisted of 146 patients divided into two groups: responders (R) and nonresponders (NR). The complete remission of T2D was achieved in 51 (34.9%) patients. There were 95 (65.1%) patients in the NR group with partial remission, improvement, or no changes in T2D. The mean follow-up was 50.0 months. In a multivariate logistic regression analysis, a T2D duration of less than 5 years was found to be a predictor to T2D remission (OR = 5.5, p = 0.002), %EWL significantly corresponded to T2D remission (OR = 1.090, p = 0009).ConclusionBariatric and metabolic surgery appears to be a good option for T2D treatment in elderly patients. A shorter duration of T2D before surgery and higher %EWL after surgery were independent predictors of T2D remission in patients over 65 years of age.Graphical abstract

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

Social dilemma analysis on vaccination game accounting for the effect of immunity waning

A new SEIRS-based ODE (Ordinary Differential Equation) model is built, where asymptomatic and symptomatic infectious compartments, hospitalized state and immune state are additionally introduced, which is dovetailed with a behavior model that defines the vaccination rate as time-variable. We also apply Social Efficiency Deficit; SED, to quantitatively identify whether or not social dilemma taking place behind the model dynamics. Numerical results prove that, depending on the fraction of asymptomatic infected individuals and the discount ratio of infected force for asymptomatic state compared with that for symptomatic one, whether or not social dilemma appearing is different, which is also substantially affected by the vaccination cost and the immunity waning rate. The behavior model tends to incur a slight social dilemma brought by wasting vaccination even in the region of disease free, identified by R0<1. Meanwhile, a relatively strong social dilemma is indicated in the parameter region where the behavior model shows less amount of vaccinated population while the social optimal state needs much more vaccinated for complete remission of disease.

Bing–Neel Syndrome and Coexisting Pituitary Macroadenoma in a Patient with Waldenström Macroglobulinemia Revealed by 18F-FDG and 68Ga-Pentixafor PET/CT

A 63-year-old man presenting with peripheral neuropathies was diagnosed of Waldenström's macroglobulinemia, and Bing-Neel syndrome was subsequently confirmed via cerebrospinal fluid examinations. Besides involvement in bone marrow, lymph nodes, as well as the thoracic and sacral nerve root, 68Ga-Pentixafor PET/CT detected active tracer uptake in bilateral choroid plexus, which was negative in 18F-FDG PET/CT, possibly suggesting the involvement of Bing-Neel syndrome. The coexisting pituitary macroadenoma was FDG-avid but negative in 68Ga-Pentixafor PET/CT. After six cycles of chemotherapy, the follow-up PET/CT showed complete remission of the previous disease, including the high uptake of 68Ga-Pentixafor in choroid plexus. However, the hypermetabolic pituitary macroadenoma remained unchanged.

Pediatric vulvar lichen sclerosus: Does it resolve or does it persist after menarche?

Although data regarding the rates of remission and progression of the disease are still scarce, it is generally now acknowledged that pediatric vulvar lichen sclerosus (pVLS) can persist beyond puberty. Recent studies reveal that this condition may persist in as many as 75% of cases. The present study aims to answer the following query: how does pVLS evolve after menarche? This observational retrospective study conducted on premenarchal girls diagnosed with pVLS in our institution between 1990 and 2011 describes 31 patients who returned for multidisciplinary clinical evaluation following menarche. The mean follow-up time was 14 years. At the post-menarche clinical examination, patients were classified as follows: 58% were still affected by VLS, 16% presented with a complete remission of disease, and 26% were completely asymptomatic although with persistent clinical signs of VLS. In our series, pVLS persists following menarche in the majority of patients. These findings suggest the importance of a long-term follow-up even among patients who report resolution of symptoms following menarche.

Perceptions and Management Practices of Onychomycosis Among Thai Physicians

Objective: To examine the proportion of physicians who conducted mycological laboratory procedures to confirm a diagnosis of onychomycosis. The secondary purpose was to evaluate the practical management of physicians, comparing general practitioners and dermatology-related physicians. Materials and Methods: This cross-sectional study and questionnaire-based research was conducted during 2021-2022. The questionnaire was composed of questions related to the practical management of onychomycosis, including diagnosis and treatment. Results: Overall, 143 physicians were recruited to take part in this study. The number of physicians who conducted direct examination with potassium hydroxide was 99 (69.2%). The number of dermatology-related physicians who conducted mycological laboratory examinations to confirm the diagnosis was significantly higher than among general physicians (95.8% vs. 52.2%; p&lt;0.001). Feet examination and determination of poor prognostic factors, such as elderly age, nail thickness, presence of dermatophytoma and nondermatophytes infection, were done by the dermatology-related physicians in significantly higher numbers. Blood testing before starting treatment for onychomycosis with oral antifungal medications seemed to be higher (87.5%) in the dermatology-related group. Moreover, mycological re-evaluation after treatment cessation was more significantly requested by the dermatologyrelated participants (75% vs. 15.8%, p&lt;0.001). Conclusion: Laboratory confirmation, feet examination, and the recognition of poor prognostic factors were significantly lower in the general practitioner group. These findings should raise awareness for improving further education about onychomycosis management in medical students, since mycological laboratory examination is crucial for diagnosis and it is helpful in guiding the proper disease management for complete disease remission.

DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation.

Esophageal cancer (ECa) is associated with high mortality, mostly due to late diagnosis, precluding curativeintent surgery. Hence, neoadjuvant chemoradiation (ChRT) is recommended in most patients regardless of histological subtype. A proportion of these patients, however, achieve complete disease remission and might be spared of radical surgery. The lack of reliable, minimally invasive biomarkers able to detect post-ChRT disease persistence is, nonetheless, a major drawback. We have previously shown that miRNA promotor methylation enables accurate cancer detection in tissues and liquid biopsies but has been seldom explored in ECa patients. Herein, we sought to unveil and validate novel candidate biomarkers able to detect ECa prior and post ChRT. Promoter methylation of miR129-2, miR124-3 and ZNF569 was assessed, using quantitative methylation-specific PCR (qMSP), in tissue samples from normal esophagus, treatment-naïve and post-ChRT ECa, as well as in liquid biopsies from ECa patients. All genes disclosed significantly different promoter methylation levels between ECa and normal esophagus, accurately detecting post-ChRT disease, especially for adenocarcinoma. Remarkably, miR129-2me /ZNF569me methylation panel identified ECa in liquid samples with 53% sensitivity and 87% specificity. MiR129-2me , miR124-3me and ZNF569me accurately discriminate ECa, either pre- or post-ChRT, from normal tissue, enabling ECa detection. Furthermore, circulalting methylation-based biomarkers are promising minimally invasive tools to detect post-ChRT residual ECa. Overall, our results encourage the use of miRNA methylation biomarkers as accurate ECa detection tools as a novel approach for ChRT response monitoring.

VERY LATE RELAPSE IN HODGKIN DISEASE: OUTCOME OF PATIENT RELAPSING MORE THAN 24 YEARS AFTER PRIMARY CHEMO- AND RADIOTHERAPY ON RARE LOCATION

Late Hodgkin disease refers to a recurrence of the disease after a period of remission (absence of disease symptoms). It can occur as a de novo (new) malignant neoplasma or as a relapse of the old disease. In some cases, late Hodgkin disease may be a new disorder that is not related to the original disease. This can occur if the patient was not properly treated for the original disease, or if the patient's immune system was compromised and developed something new. In other cases, late Hodgkin disease may be a relapse of the original disease. This means that the disease has come back after a period of remission. We present a case of a 27-year-old male with HD after 24 years of period of complete remission of the initial disease. This very rare relapse of HD was presented on gingivae like an extranodal involvement which is less commonly found than in other lymphomas. The histopathological analysis of the gingivae during the relapse showed presence of another subtype of Hodgkin disease - nodular lymphocyte predominant (NLPHL) on a rare location. It is important for patients to follow their treatment plan closely and to continue to see their healthcare provider for follow-up care after treatment. Our case illustrates that Hodgkin lymphoma can also appear in soft tissue masses such as gingivae and is more refractory to the standard therapeutical approach.