Pulse Therapy Research Articles

Suspicious of Acute Kidney Graft Rejection: Tacrolimus Pharmacokinetics Under Methylprednisolone Therapy.

Acute rejection remains one of the main complications in the first months after transplantation and may influence long-term outcomes. Tacrolimus has proven its usefulness in solid organ transplants and its monitoring through the application of pharmacokinetic concepts to optimize individual drug therapy. This research proposes to evaluate the tacrolimus pharmacokinetic parameters in patients suspected of acute kidney graft rejection under methylprednisolone pulse therapy. Eleven adult tacrolimus-treated renal recipients were selected from a prospective, single-arm, single-center cohort study, with suspicion of acute rejection although in use of methylprednisolone pulses therapy. They were followed up for three months posttransplantation, being tacrolimus trough serum concentrations determined using a chemiluminescent magnetic immunoassay, and pharmacokinetic parameters were estimated by using a nonlinear mixed-effects model implemented by Monolix 2020R1. A tacrolimus trough serum concentration range of 8 to 12 ng.mL-1 was considered therapeutic. Six patients showed acute cellular rejection, and two of them in addition had an antibody- mediated rejection. Tacrolimus trough serum concentration was below the reference range in eight patients. Most patients showed a high tacrolimus concentration intrapatient and pharmacokinetic parameters variability. The obtained pharmacokinetics parameters helped in understanding the kidney recipient patients' tacrolimus behavior, assisting in the improvement of individual drug therapy and reducing the risk of acute rejection episodes.

Donor-derived cell-free DNA versus left ventricular global longitudinal strain in noninvasive detection of heart allograft injury

Abstract Introduction Invasive endomyocardial biopsy (EMB) is still considered the gold standard method for monitoring heart transplant (HTx) rejection. However, it is associated with potentially serious complications, and its histopathologic interpretation has high interobserver variability. Thus, noninvasive methods for surveillance of the transplanted organ remains of great interest. The noninvasive donor-derived cell-free DNA is a marker of graft injury which can indicate acute rejection, even before the histopathological diagnosis of rejection detected by EMB. The assay has a high negative predictive value for acute rejection. Left ventricular global longitudinal strain (LV GLS) is an emerging marker of subclinical myocardial injury which plays a crucial role in the evaluation of several cardiac diseases; however, its role in HTx injury has so far been poorly investigated. Purpose We aimed to investigate the efficacy of a local laboratory-run dd-cfDNA assay-based heart transplant rejection surveillance programme, and the prognostic and discriminatory performance of LV GLS for subsequent heart allograft injury. Methods HTx recipients without a history of allograft rejection requiring intensification of immunosuppressive therapy were transitioned from our EMB-based surveillance protocol to dd-cfDNA-based rejection surveillance. We assessed the percentage of dd-cfDNA to total cell-free DNA. Injury cut-off was defined by a dd-cfDNA level ≥0.20%, while the severe injury threshold was at ≥0.35%. LV ejection fraction was calculated using 2D Simpson’s method. To derive LV GLS, we analyzed apical 4-chamber, 2-chamber, and long-axis images by 2D speckle tracking echocardiography. Results A total of 244 dd-cfDNA samples were analyzed from 46 patients in fifteen runs performed monthly between October 2022 and December 2023. The dd-cfDNA fraction remained below the injury cut-off in most patients (81%). There were no missed rejection episodes. 88% of routine EMBs that would have otherwise been performed were safely avoided. Eighteen for-cause EMBs were performed based on dd-cfDNA levels suggesting injury. One EMB verified moderate cellular rejection (ISHLT grade 2R) that required steroid pulse therapy. Two EMBs proved mild cellular rejection, one EMB confirmed mild antibody-mediated rejection, while one EMB proved mixed rejection. Thirteen EMBs found no rejection. Mean LVEF was preserved (57.6%±7.6%). Mean LV GLS was -15.1%±2.5% in the whole cohort, while -15.6%±4.7% in recipients with HTx rejection on indication EMB. There was no significant correlation between dd-cfDNA and LV GLS (n=159). Conclusion The noninvasive dd-cfDNA assay is effective in ruling out acute rejection and safely decreases the necessity of invasive surveillance EMBs after HTx. LV GLS is less sensitive in comparison with the dd-cfDNA assay for detection of myocardial injury in the early stages of graft rejection in HTx recipients at low risk for rejection.

Polymyalgia rheumatica and giant cell arteritis: diagnosis and management.

There have been advances in the diagnosis and treatment of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). Themes in PMR and GCA include classification criteria, ultrasound imaging of temporal and axillary arteries replacing biopsies for diagnosis of GCA, faster diagnosis and treatment with rapid access clinics for suspected GCA, and expanding treatment options with the goal of rapid suppression of inflammation and sparing steroids. Treatment is aimed at suppressing inflammation quickly in both GCA and PMR. Randomized trials have demonstrated success in reducing glucocorticoids when adding advanced therapies such as interleukin 6 (IL6) inhibitors. Other treatments including Janus kinase (JAK) inhibitors (especially a phase 3 trial of upadacitinib at 15 mg daily and secukinumab (an IL17 inhibitor) are being tested. Some uncontrolled GCA protocols are limiting glucocorticoids to initial IV pulse therapy only or rapid tapering of oral glucocorticoids with upfront treatment with tocilizumab. There is uncertainty of who should have an advanced therapy and how long to use it for and what order to consider advanced therapies when treatment fails. In PMR, studies are performed when patients cannot taper glucocorticoids effectively, whereas in GCA, advanced therapies are started with disease onset or with recurrent GCA.

Long-term outcomes of intravenous corticosteroid pulse therapy for rapidly progressive alopecia areata: A single-center retrospective analysis of 106 cases and usefulness evaluation of a scoring system originally designed for half-year efficacy prediction for extended periods.

Intravenous corticosteroid pulse therapy (IVPT) has been preferentially conducted for rapidly progressive alopecia areata (RP-AA); however, the evaluation of long-term outcomes has been insufficient. In this study, 106 IVPT-treated RP-AA patients (36 males and 70 females) who were followed up for more than 1 year and up to 6.8 years were retrospectively analyzed. The mean observation period was 1137.8 ± 587.9 days (range 380-2490). The mean severity of alopecia tool (SALT) score before IVPT was 21.3 ± 23.4 but whole-scalp hair loss was observed in all cases after the intervention, suggesting that IVPT was performed soon after the onset. With additional interventions represented by intralesional triamcinolone acetonide injection with or without topical potent corticosteroid for those who insufficiently responded at 6 months after IVPT, 64.2%, 14.2%, and 21.7% of the patients respectively achieved good response (GR; SALT score ≤25), moderate response (MR; 25 < SALT score <75), and poor response (PR; 75 ≤ SALT score) 1 year after IVPT. On the final evaluation, the proportions of patients with GR, MR, and PR were 79 (74.5%), 7 (6.6%), and 20 (18.9%). Sixteen patients achieved and maintained full hair regrowth with IVPT alone until the end of observation. A previously reported scoring system for the short-term outcome prediction was shown to be useful for distinguishing the final-point GR responders from PR responders (P = 0.003). Of note, 21 patients were found to have some symptoms suggestive of the existence of preceding infectious diseases and tended to relapse. The revised scoring system adding the absence of preceding infectious diseases as one factor successfully predicted the occurrence of the relapse in our cohort (P = 0.002). Taken together, previously unreported real-world efficacy of IVPT to RP-AA was elucidated with the invention of a tool putatively enabling optimal long-term management.

Steroid response in a rare case of vertebrae butterfly with spinal cord compression caused by chronic subdural hematoma

IntroductionSpinal subdural hematoma (SSH) is a rare entity. Clinical symptoms include motor, sensory and/or autonomic dysfunction due to compression of the spinal cord. There is no standard consensus in the management of SSH. Here, we report a rare case of SSH of sudden onset following trauma, successfully treated with conservative therapy.AimThis case highlights butterfly vertebrae as an incidental imaging finding before SSH diagnosis.Case studyA 30-year-old female presented with weakness in the lower extremities after trauma, accompanied by paresthesia, urinary retention, and impaired defecating function. The thermoregulatory sweat exam revealed sudomotor dysfunction. Multiple slice computed tomography (MSCT) examination of the whole spine revealed wedge deformity of vertebral corpus (VC) L4 on the right lateral side, and VC L5 butterfly vertebrae. Spine magnetic resonance imaging (MRI) revealed an extramedullary intradural lesion at the T7 to T10 level suggestive of subdural hematoma.Results and discussionThe administration of methylprednisolone pulse therapy, combined with physical rehabilitation, led to a rapid and significant improvement in the patient's motor function. The absence of the spinal pain possibly indicated that there was no more extension of the hematoma; motor recovery, even if slight, should be a predictor of successful conservative therapy, and physical rehabilitation.ConclusionsSSH is an uncommon condition, with varying clinical presentation, and progression. This case report highlights significant improvement following conservative steroid treatment of a SSH. It also highlights a unique incidental finding of butterfly vertebra in a patient with paraparesis following trauma.

Patients with anti-small ubiquitin-like modifier activating enzyme-positive dermatomyositis resembling antisynthetase syndrome with poor prognosis: a bicentric international retrospective study and literature review.

This study aimed to describe adult Brazilian and Japanese patients with anti-small ubiquitin-like modifier activating enzyme (SEA)-positive dermatomyositis (DM), as there are few studies in the literature. A literature review was also conducted. This bicentric international retrospective study, conducted between 2012 and 2023, included patients with anti-SAE-positive DM (2017 European League Against Rheumatism/American College of Rheumatology classification criteria). All demographic features and clinical, laboratory, therapeutic, and follow-up data were collected from Brazilian and Japanese centers using pre-standardized and parameterized information. We included 17 adult patients with a median age of 65 (56-76) and a predominance of females (82.4%). Constitutional symptoms at baseline were present in 58.8% of the patients. In addition to classical cutaneous DM lesions, one-third of the patients had myalgia and significant muscle weakness, whereas half presented with dysphagia, interstitial lung disease, and joint manifestations. The first-line treatment consisted of intravenous methylprednisolone and immunoglobulin pulse therapy in 41.2% and 28.6% of the patients, respectively. The median follow-up duration was 20 (13-74) months; at the last medical evaluation, half had active disease and were still using oral glucocorticoids (median dosage, 10.0 mg/day). Approximately one-fifth to one-third of the patients were diagnosed with different types of cancer, had severe infections, or died. Patients with anti-SAE-positive DM not only resemble the phenotype of antisynthetase syndrome but are also associated with a poor prognosis.

Angioinvasive Rhino-Orbital-Cerebral Mucormycosis in a Patient with Type 2 Diabetes Mellitus: A Complex and Lethal Cause of Stroke

Rhino-orbital-cerebral mucormycosis is a rapidly progressive and often fatal fungal infection caused by molds of the order Mucorales, particularly affecting immunocompromised individuals. This infection is notorious for its angioinvasive properties, enabling the fungi to invade blood vessels and leading to tissue necrosis. We report the clinical course of a 59-year-old Caucasian man with poorly controlled type 2 diabetes (HbA1c 16.8%) who presented with unilateral headache, left-sided facial numbness, and incomplete left ocular motor paresis. Initial presentation raised suspicion of orbital phlegmon, leading to antibiotic and later corticosteroid pulse therapy, which worsened the patient’s condition. Subsequent imaging demonstrated extensive inflammatory changes, including wall irregularities of the left intracranial internal carotid artery, accompanied by ocular protrusion and periorbital enhancement. New palatal lesions indicated mucormycosis, which was confirmed by molecular analysis of a palatal biopsy, leading to Amphotericin B treatment. Pre-surgery imaging revealed a malignant middle cerebral artery infarction, and the patient died 16 days after symptom onset and 12 days after initial presentation under palliative care due to a poor prognosis. This case of angioinvasive mucormycosis underscores the severe and often fatal course of rhino-orbital-cerebral mucormycosis in an immunocompromised individual. The rapid progression from initially vague and unspecific symptoms to extensive vascular involvement and stroke highlights the critical need for early and accurate diagnosis, as well as prompt intervention to prevent further disease progression. Additionally, this case also illustrates the potential risks associated with corticosteroid therapy in the presence of undiagnosed fungal infections, which can exacerbate the condition and lead to serious complications. Clinicians should maintain a high index of suspicion for mucormycosis in similar clinical scenarios, prioritizing adequate antifungal treatment and careful monitoring to improve patient outcomes. Early interdisciplinary collaboration is essential for the effective management of such complex cases.

8220 Panhypopituitarism due to Granulomatosis with Polyangiitis - Wegener's Granulomatosis. A Very Rare Cause of Panhypopiturism: A Case Report

Abstract Disclosure: T.D. Bertolacini da Silva: None. V.S. da Silva: None. P.R. Fiorin: None. J.S. Freire: None. C.G. Braga: None. M. Canzian: None. C. Machado: None. Background: Granulomatosis with Polyangiitis (GPA) is a necrotizing granulomatous vasculitis and pituitary involvement is less than 1%. We report a case of pituitary involvement, with CDI, and later panhypopituitarism. Clinical Case: A 43-year-old man was admitted in a hospital due to a headache 3 months ago. CT showed an expansive lesion in posterior fossa and hydrocephaly. Submetted for withdrawal of a Schwannoma and peritoneal shunt, with ipsilateral peripheral facial paralysis. After 1 year, started with polyuria and polydipsia, CDI was diagnosed and DDAVP started. Pituitary MRI showed a small rounded image in the sella turcica, cystic, 0.8 x 0.5 x 0.8cm. After 6 months, readmitted on hospital after trauma in surgical scar, with abscess, accomplished debridement and started oxacillin, with good controls of electrolytes and diuresis: Na 144 mmol/L (137-145 mmol/L). Readmitted after 2 months for surgical wound infection, on that occasion hyponatremia was diagnosed. Other tests were requested: TSH &amp;lt; 0.0015 uIU/mL (0.49-5.58 uIU/mL/mL), free T4 0.68 ng/dL (0.89-1.53 ng/dL), repeated TSH 0.036 uIU/mL and free T4 0.63 ng/dL, central hypothyroidism has been confirmed and levothyroxine started. Pituitary MRI was repeated with enlarged adeno-pituitary: 1.9 x 1.7 x 1.1cm, extension to the suprasellar cistern, compression, and superior displacement of the optic chiasm. Other tests: GH 0.173 ng/mL (&amp;lt; 3 ng/mL), IGF1 66 ng/mL (58-219 ng/mL), testosterone &amp;lt; 7.30 ng/dL (12-59 ng/dL), LH 0.1 mIU/mL (1.9-12.5 mIU/mL), prolactin 0.66 ng/mL (2.1-17.7 ng/mL), ACTH 6.66 pg/mL (&amp;lt; 46.0 pg/mL), confirmed pan-hypopituitarism. After 1-month patient started with petechiae and persisted with hyponatremia, SIADH hypothesis made. Chest CT showed a solid pulmonary nodule, spiculated, 2.6 x 2.1 x 1.8cm, first biopsy was inconclusive. After repeating the chest CT there was persistence the pulmonary nodule 4.2 x 5.8 x 4.4cm. Videothoracoscopy was perfomed and anatomopathological confimed GPA and C-ANCA positive. The patient received prednisone, ivermectin, pulse therapy (methylprednisolone) and cyclophosphamide. After 8 months admitted on hospital due to pneumonia and exogenous Cushing's syndrome, new tests were requested: pituitary MRI showed a hypocontrasting and heterogeneous on the sellar cavity 0.4 x 0.7 x 1.0cm, showing reduction of the lesion after treatment of the rheumatological disease. Patient also received treatment with Rituximab and the last pituitary MRI: hypocontrasting lesion, sometimes with a cystic appearance in the sellar cavity. Currently, in use: testosterone replacement, desmopressin prednisone, levothyroxine, rosuvastatin/ezetimib, cholecalciferol, colchicin and ibandronate sodium. He presented with an improved quality of life. Conclusion: GPA should be considered in cases of CDI and hypopituitarism when sellar disorders were discarded, and if a vasculitis is suspected. Presentation: 6/1/2024

8043 IgG4-related disease with isolated involvement of the pituitary gland: case report

Abstract Disclosure: J.M. Ramos: None. Female patient, 36 years old, presented to our service complaining of a headache lasting five weeks, mainly in the frontal and left periorbital region, radiating to the occipital region. The pain was intense and intermittent, lasting about 40 minutes. No nausea or vomiting was reported, but the patient experienced dizziness and double vision. During the symptomatic interview, the patient mentioned increased thirst and urinary volume. In her medical history, she denied comorbidities, with only frequent episodes of tension-type headaches. She had no continuous medication use and no known drug allergies. The patient had undergone two cesarean sections, with the last one in December 2021. On physical examination, she had horizontal binocular double vision in all three gazes to the left, accompanied by pain during eye movement. Increased facial sensitivity on the left in branches V1 and V2 was observed. The rest of the physical examination showed no abnormalities. Initial general laboratory tests were normal. Evaluation of pituitary function was mostly normal, except for slightly elevated prolactin. A cranial MRI revealed an expansive lesion with sellar and suprasellar components measuring 1.2x1.1x1.2cm. Additional imaging of the sella turcica showed an intra- and suprasellar expansive lesion, predominantly isointense on T1, hyperintense on T2, with discreetly heterogeneous enhancement with gadolinium. In consultation with the neuroradiology team, a hypointensity on T2 at the left margin of the pituitary was noted, suggesting an inflammatory etiology. Based on this, laboratory tests were conducted, and treatment with methylprednisolone 1g per day for 7 days was initiated. After treatment completion, the IgG4 level was found to be 146.7 mg/dL (upper limit of reference: 86 mg/dL). A follow-up MRI, five days after the steroid pulse therapy, showed a reduction in lesion size to 0.8 cm in the cranio-caudal dimension, with a preserved appearance of the optic chiasm. The patient experienced considerable symptom improvement and was discharged with oral corticosteroids and a scheduled initiation of rituximab. The patient meets criteria confirming the diagnosis of IgG4-related hypophysitis, a rare condition representing 30% of hypophysitis cases. Isolated pituitary involvement is even rarer, and its association with diabetes insipidus has been described. Treatment involves corticosteroids, and rituximab can be considered, especially in recurrent cases. Presentation: 6/3/2024

A case of immune checkpoint inhibitor-associated hemophagocytosis after initiation of atezolizumab plus bevacizumab therapy for advanced hepatocellular carcinoma.

A woman in the 70s with a decreased appetite and weight loss (4kg) in the last 3months was referred to our hospital. An enhanced CT scan of the abdomen showed a hepatocellular carcinoma (HCC) of 83mm in diameter of the liver with metastasis to the para-aortic lymph nodes, the left adrenal gland, and the right lower lung lobe (cStage IVb). She was started on atezolizumab + bevacizumab (Atezo-Bev) therapy. A week after the treatment, she began to have a decreased appetite, fever in the 39°C range, subcutaneous bleeding, and a slight headache when walking. So she was urgently admitted to our hospital. We diagnosed her as having a hemophagocytic syndrome and administered 1g steroid pulse therapy for 3days followed by 1mg/kg of prednisone. Her condition began to improve. This is the first case report of a hemophagocytic syndrome in a patient with HCC treated with Atezo-Bev.

Acute autoimmune hemolytic anemia in a patient with systemic lupus erythematosus

Introduction Autoimmune hemolytic anemia occurs due to the accelerated destruction of erythrocytes as a result of the dysfunction of immune system cells, which produce antibodies against the normal antigens of the membrane of hematopoietic cells. One of its causes is systemic lupus erythematosus. Materials and methods We present a case of a 20-year-old patient who was hospitalized with acute autoimmune hemolytic anemia, having been diagnosed with SLE at the age of 18 years. At the onset of the disease, hemolytic anemia was a differential diagnostic challenge. Results The differential diagnosis between primary and secondary autoimmune hemolytic anemia (AIHA) was an important step. The presence of antinuclear antibodies (ANA Hep2, Anti-dsDNA, Anti-cardiolipin, Anti-phospholipids, anti-Ro, Anti-Sm B) were important arguments in making the diagnosis. The relapse of AIHA was caused by inadequate treatment, due to a lack of compliance. Pulse therapy combined with methylprednisolone and cyclophosphamide successfully resolved the AIHA. Conclusions Hematological abnormalities are commonly seen in SLE patients, but hemolytic autoimmune anemia is a rare condition. A timely diagnosis of the cause of hemolytic anemia and proper treatment of lupus by correcting autoimmune disorders are crucial in disease management. Pulse therapy combined with corticosteroids and immunosuppressants is effective in acute relapses of hemolytic anemia.

C1q-Fixing De Novo Donor Specific Antibodies in Therapeutic Management of Chronic Antibody-Mediated Rejection Postkidney Transplantation

Evidence for C1q-fixing donor-specific antibodies (DSA) after chronic antibody-mediated rejection (CABMR) treatment is lacking. We investigated if C1q-DSA could predict therapy response in patients with biopsy-proven CABMR. Twenty kidney transplant patients with late-onset DSA were enrolled. Patients with biopsy-proven CABMR received three plasma pheresis sessions, one dose of rituximab (375 mg/m2), and steroid pulse therapy. We monitored IgG-DSA, C1q-DSA, and renal graft function for >2 years post-CABMR treatment. Patients with C1q-DSA mean fluorescence intensity (MFI) decreased by less than 50% post-treatment were classified as C1q-nonresponders. We compared Banff classification scores (g, ptc, cg, c4d) before and 6 months after treatment. Fourteen (70%) of 20 patients were C1q-DSA positive. The MFIs of IgG-DSA and C1q-DSA before treatment were significantly higher in the C1q-DSA positive group than in the negative group, at 20,035 and 10,918 (P = .008) and 17,702 and 21 (P < .001), respectively. Fifteen patients (75%) were diagnosed with CABMR via biopsy, and 12 patients received rejection therapy. Five (41.7%) patients were C1q-responders and seven (58.3%) were C1q-nonresponders. The MFIs of C1q-DSA before treatment were not significantly different between the two groups (11,521 vs. 13,985). Renal graft function was stable after treatment in C1q-responders for 3 years. In contrast, renal graft function tended to deteriorate in C1q-nonresponders. Biopsy showed improvement in scores in 75% of C1q-responders while deterioration in scores in 42.9% of C1q-nonresponders. C1q-DSA may be a good predictor of outcomes after CABMR treatment.

Management of anti-melanoma differentiation-associated gene 5 antibody-induced refractory dermatomyositis complicated by interstitial pneumonia using tofacitinib and its outcomes: a case report

BackgroundClinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined.Case presentationA 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient’s respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, βD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis.ConclusionThe patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected.

Rectum necrosis in a patient with severe COVID19 infection after CAR-T therapy: a case report

BackgroundCoronavirus disease 2019 (COVID19) can cause gastrointestinal complications as well as respiratory tract disease. Coagulation abnormalities and thrombosis frequently occur in COVID19, especially in cases with severe clinical outcome. The relationship between gastrointestinal perforation and coagulopathy due to COVID19 remains unclear.Case presentationA 49-year-old female received Chimeric antigen receptor T (CAR-T) therapy for an early recurrence of diffuse large B-cell lymphoma (DLBCL) that was refractory to chemotherapy. She was diagnosed with cytokine release syndrome (CRS) because of a fever and oxygen desaturation, and administered tocilizumab. Forty days after completing CAR-T therapy, she was infected with COVID19 and transferred to our hospital. Her general condition worsened and she developed COVID19 pneumonia, and then steroid pulse therapy was started. While her respiratory condition improved, she experienced pain in the anal region and computed tomography (CT) revealed a rectal perforation. An emergency surgery was undertaken, and the lower rectum wall was found to be completely necrotic. Removal of the necrotic part of the rectum tissue, and drainage and lavage of necrotic tissue in the pelvic cavity were performed. The remaining rectum was resected with partial sigmoidectomy, but we could not make the anal stump closed. In addition, an end colostomy in the sigmoid colon was performed. Histopathological findings showed thromboses in the rectal mesentery veins. After the first surgery, the pelvic abscess cavity persisted and her high-grade fever continued. Reoperation was laparoscopically performed, and she underwent a resection of anal canal with residual necrotic rectal and mesorectal tissue, and a drainage of the pelvic abscess. After the reoperation, her general condition improved and CT showed that the abscess cavity had significantly improved.ConclusionsGastrointestinal perforation, especially rectal necrosis due to coagulopathy caused by severe COVID19 infection, is a rare but life-threatening complication. Physicians should have a high degree of clinical suspicion for timely diagnosis and management, and surgical intervention is necessary in cases of rectal necrosis.

Steroid pulse therapy in idiopathic nephrotic syndrome in the era of modern immunosuppressive treatment-still up to date?

Intravenous steroid pulses (SP) are successfully used for the treatment of patients with idiopathic nephrotic syndrome (INS) resistant to oral prednisone. We performed a retrospective analysis of all patients in the three pediatric nephrology centers of the Paris region from 2002 to 2022 who were resistant to a 30-day course of oral prednisone and who received SP for their first INS flare and analyzed their disease course over 4years. Forty-seven patients (17 girls), median age 3.4years, were analyzed. Of them, 68% reached remission within 7days of SP. No significant short-term side effects were noted. Half of the patients started immunosuppressive treatment immediately after their first remission and 62% of them relapsed at least once, whereas all the patients who did not receive immunosuppressive treatment since their first remission relapsed. Among the SP-sensitive patients, 75% needed calcineurin inhibitor (CNI) or B-cell depletion during their disease course to achieve stable remission. Forty-two percent of the whole cohort received B-cell-depleting agents. Among the 15 SP-resistant patients, all received CNI. Twelve/fifteen patients reached remission. After 4years, 68% among the SP-sensitive patients and 87% of SP-resistant patients still had an active disease. SP are helpful to obtain rapid remission in pediatric INS patients resistant to oral steroids. However, as most SP-sensitive patients need immunosuppressive drugs, mainly CNI and B-cell-depleting agents it could be interesting to discuss the possibility to start CNI directly after the 30-day course of prednisone instead of SP.

Predictive factors for treatment response in active thyroid eye disease

Introduction/objectiveActive moderate-to-severe thyroid eye disease (TED) is a major therapeutic challenge. Pulse therapy with intravenous glucocorticoids is the standard treatment, with variable response. Radioactive iodine therapy (RAI) was reported as a risk factor for onset or worsening of TED. We evaluated putative predictive factors for response to intravenous methylprednisolone in patients with active TED. MethodsData were collected for 64 consecutive patients (45 women) with active moderate-to-severe TED treated with a minimum cumulative dose of 4.5g methylprednisolone. Patients were classified as responders (R) or non-responders (NR) on Clinical Activity Score (CAS), and clinical features were compared between groups. ResultsSixty-two patients had Graves’ disease (GD), and 2 had Hashimoto's thyroiditis (HT). Median age at thyroid dysfunction diagnosis, TED manifestation and pulse therapy was 46, 48 and 51 years, respectively; 56.2% were euthyroid when TED manifested. Among them, 73.4% were responders. R and NR were comparable for gender, age, thyroid function, serum antibodies, disease duration, pre-treatment CAS, smoking, lipid profile, and adverse events. Forty-nine patients were treated with RAI for GD: 15 before the active phase of TED (before pulse therapy), 16 during, 17 after, and 1 both before and after pulse therapy. Response rate was higher in patients who received RAI during than after pulse therapy (P=0.032) and similar to those not treated with RAI at all (P=0,599). ConclusionPulse therapy was effective in the majority of patients. The only factor associated with response to pulse therapy was the timing of RAI, suggesting that it seems to be safe when used concomitantly with pulse therapy.

Cytokine release syndrome following COVID-19 infection during treatment with nivolumab for cancer of esophagogastric junction carcinoma: a case report and review

BackgroundCytokine release syndrome (CRS) is an acute systemic inflammatory syndrome characterized by fever and multiple organ failure, which is triggered by immunotherapy or certain infections. Immune checkpoint inhibitors rarely cause immune-related adverse event- cytokine release syndrome (irAE-CRS). This article presents a case report of irAE-CRS triggered by coronavirus disease 2019 (COVID-19).Case presentationA 60-year-old man with type 2 diabetes received nivolumab treatment for esophagogastric junction carcinoma and experienced two immune-related adverse events: hypothyroidism and skin disorder. Eleven days before his visit to our hospital, he had a fever and was diagnosed with COVID-19. Five days before his visit, he developed a fever again, along with general malaise, water soluble diarrhea, and myalgia of the extremities. On admission, the patient was in a state of multiple organ failure, and although the source of infection was unknown, a tentative diagnosis of septic shock was made. The patient's condition was unstable despite systemic management with antimicrobial agents, high-dose vasopressors, and intravenous fluids. We suspected CRS due to irAE (irAE-CRS) based on his history of nivolumab use. Steroid pulse therapy (methylprednisolone 1 g/day) was started, and the patient temporarily recovered. However, his respiratory condition worsened; consequently, he was placed on a ventilator and tocilizumab was added to the treatment. His muscle strength recovered to the point where he could live at home, and was subsequently discharged.ConclusionIn patients previously treated with immune checkpoint inhibitors, irAE-CRS should be considered as a differential diagnosis when multiple organ damage is observed in addition to inflammatory findings. It is recommended to start treatment with steroids; if the disease is refractory, other immunosuppressive therapies such as tocilizumab should be introduced as early as possible.

High-frequency irreversible electroporation ablation for the prostate in Beagle dogs.

Ablation procedures have garnered significant attention as a minimally invasive treatment of prostate diseases. However, the feasibility and safety of applying high-frequency irreversible electroporation (H-FIRE) to ablate the Beagle prostate for benign prostatic hyperplasia (BPH) treatment have not been thoroughly explored, the appropriate range of parameters has not been determined. In order to ensure the feasibility and safety of prostate ablation surgery, we conducted a study using Beagle dogs as subjects to investigate prostate tissue. We utilized a composite steep pulse therapy device to perform ablations on 26 lateral lobes of the prostate in 13 Beagles, employing various parameters for different needle distances. The effectiveness of this device was assessed through the observation of the ablation area, intraoperative muscle tremors, postoperative hematological examination, and gross inspection. The findings of our study revealed that 1,000 to 2,000 v/cm in electric field strength, combined with 5 µs pulse width and pulse number 100, is a safe parameter range for ablation of prostate tissue. At the same time, the large electric field strength (2,000 v/cm) has the best ablation effect with the biggest continuous and thorough ablation area. All parameters of H-FIRE were safe for Beagles. H-FIRE ablation for prostate is safe and effective in dogs, which has the potential to be a useful addition to the range of minimally invasive treatments available for the treatment of BPH against this backdrop of increasing surgical practice.

410.1: The effect of steroid pulse therapy for the reduction of acute rejection episode in subclinical borderline changes: An open-label, randomized clinical trial.

410.1: The effect of steroid pulse therapy for the reduction of acute rejection episode in subclinical borderline changes: An open-label, randomized clinical trial.

Therapeutic agents for steroid-refractory immune checkpoint inhibitor-related myocarditis: a narrative review.

Immune checkpoint inhibitors (ICIs) have become one of the cornerstones of current oncology treatment, and immune checkpoint inhibitor-related myocarditis (IRM) is the most fatal of all immune checkpoint inhibitor-related adverse events (irAEs). Methylprednisolone pulse therapy (500-1,000 mg/day) is the initial treatment for IRM recommended by almost all relevant guidelines. However, subsequent treatment regimens remain unclear for patients who do not respond to methylprednisolone pulse therapy (who are defined as steroid-refractory patients). We propose a potential treatment approach for steroid-refractory IRM. The PubMed and the Cochrane Library databases were searched using keywords related to IRM. Relevant English-language articles published from January 2000 to February 2024 were included in this narrative review. Abatacept is the preferred choice for the treatment of isolated steroid-refractory IRM. For rapidly progressive or interleukin-6 abnormally elevated steroid-refractory IRM, alemtuzumab or tocilizumab/tofacitinib are the preferred therapeutic agents, respectively. For steroid-refractory IRM comorbid with myositis or comorbid with myasthenia gravis, abatacept + ruxolitinib/mycophenolate mofetil (MMF)/intravenous immunoglobulin (IVIG), or MMF + pyridostigmine/IVIG are the preferred therapeutic agents, respectively. The pathogenesis of steroid-refractory IRM and the treatment regimen remain unclear. A large number of studies need to be conducted to validate or update our proposed treatment approach.