Rapid Clinical Response Research Articles

It takes more than a machine: A pilot feasibility study of point-of-care HIV-1 viral load testing at a lower-level health center in rural western Uganda.

Barriers continue to limit access to viral load (VL) monitoring across sub-Saharan Africa adversely impacting control of the HIV epidemic. The objective of this study was to determine whether the systems and processes required to realize the potential of rapid molecular technology are available at a prototypical lower-level (i.e., level III) health center in rural Uganda. In this open-label pilot study, participants underwent parallel VL testing at both the central laboratory (i.e., standard of care) and on-site using the GeneXpert HIV-1 assay. The primary outcome was the number of VL tests completed each clinic day. Secondary outcomes included the number of days from sample collection to receipt of result at clinic and the number of days from sample collection to patient receipt of the result. From August 2020 to July 2021, we enrolled a total of 242 participants. The median number of daily tests performed on the Xpert platform was 4, (IQR = 2-7). Time from sample collection to result was 51 days (IQR = 45-62) for samples sent to the central laboratory and 0 days (IQR = 0-0.25) for the Xpert assay conducted at the health center. However, few participants elected to receive results by one of the expedited options, which contributed to similar time-to-patient between testing approaches (89 versus 84 days, p = 0.07). Implementation of a rapid, near point-of-care VL assay at a lower-level health center in rural Uganda appears feasible, but interventions to promote rapid clinical response and influence patient preferences about result receipt require further study. Trial registration: ClinicalTrials.gov Identifier: NCT04517825, Registered 18 August 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04517825.

Caplacizumab as rescue therapy in refractory TTP involving neurologic features

BackgroundThe role of caplacizumab in the routine treatment of immune thrombotic thrombocytopenic purpura (iTTP) remains to be established. Case summaryA 56-year-old woman was transferred to our center with iTTP and neurologic features. At the outside hospital, she was initially diagnosed and managed as Immune Thrombocytopenia (ITP). Upon transfer to our center, daily plasma exchange, steroids, and rituximab were initiated. After an initial improvement, refractoriness became evident with a decline in platelet count and continued neurologic abnormalities. Initiation of caplacizumab resulted in rapid hematologic and clinical responses. ConclusionCaplacizumab is a valuable treatment modality in iTTP, particularly in cases associated with refractoriness or neurologic features.

P461 Rapid response to appendectomy in the majority of patients with refractory Ulcerative Colitis

Abstract Background Appendectomy is suggested to improve the course of the disease in many patients with refractory Ulcerative Colitis (UC). Present prospective observational study demonstrates short-term outcomes after an appendectomy in 16 patients with refractory UC. Methods Between 5/2022 and 11/2022, 16 selected patients underwent appendectomy for refractory UC. Only patients with dysplasia or cancer were excluded. However, an appendectomy was not proposed to patients with severe sarcopenia or severe anemia, except in one case of severe acute colitis. The appendectomy was performed without the removal of the cecal base. Results Mean age was 35 years (18 to 59 years), there were 9 male patients. Nine had a pancolitis. Eight patients were referred to colectomy (50%). Eight were taking steroids (10mg to 75mg), all but three were under biological treatment. Median preoperative Mayo score was 6.5. Two patients had severe anemia (hemoglobin <10 g/dl). The appendix appeared to be inflamed visually in 3 patients (19%) and histologically in 10 patients (62%). Hospital stay was median 2 days, there was one wound infection at the port site. A significant improvement of disease symptoms was reported by 14 patients during the first 2 weeks. At the end of the follow-up period of 1 to 6 months, no colectomy has been performed. Conclusion The majority of patients with refractory UC demonstrates rapid clinical response to an appendectomy. Longer observation is necessary in order to determine whether the rapid response translates to a favourable long-term outcome.

106 A CASE OF COMPLETE ATRIOVENTRICULAR BLOCK AND ALTERNATING BUNDLE BRANCH BLOCK DUE TO FULMINANT MYOCARDITIS

Abstract A 41-year-old man, without previous cardiological history, presented at the emergency department with hypotension and multi-organ failure. Laboratory testing showed elevated white cell blood count (16780/mcL; normal value 4000-11000/mcL; 90% neutrophils), high-sensibility troponin I (23247 ng/L; normal value <18 ng/L) and NT-pro-BNP (21914 pg/mL; normal value <300 pg/mL). At electrocardiogram (EKG) there was sinus rhythm with complete atrioventricular block and alternating right and left bundle branch block. Echocardiography revealed a moderate left ventricular (LV) dilatation, mild LV hypertrophy, severe biventricular dysfunction (LV Ejection Fraction - EF - 30%) with dense spontaneous echo contrast and moderate pulmonary hypertension (systolic pulmonary artery pressure 51 mmHg). After positioning a temporary pacemaker, the patient was transferred to our Cardiac Intensive Care Unit. After initial hemodynamic stabilization with endovenous inotropes, diuretics, and mechanical circulatory support (intra-aortic balloon pump), coronary angiography was performed showing normal coronary arteries. Since fulminant myocarditis was suspected and magnetic resonance was not feasible due to the patient's instability, an endomyocardial biopsy (EMB) was performed with the evidence of myocardial edema, initial myocardial fibrosis, and the concomitant presence of lymphocytic and eosinophilic endo-myocarditis (despite normal eosinophilic blood count) without evidence of active viral replication. After careful exclusion of latent or active infections, high doses of corticosteroids and azathioprine were initiated, with rapid laboratoristic and clinical response. EKG showed AV block regression and QRS width's normalization, so the pacemaker was removed. LVEF rapidly improved and was completely normalized at discharge after two weeks. In the early follow-up, a cardiac magnetic resonance (CMR) was performed with evidence of persistency of mildly dilated LV, normalization of LV wall thickness and biventricular function, a diffuse increase of T1 relaxation time, increased T2 signal of the anterior and septal walls, and intramural anteroseptal late gadolinium enhancement (LGE). Fulminant myocarditis is a rare presentation of acute myocarditis, with low incidence but high mortality. The inflammation of the myocardium itself leads to acute heart failure, cardiogenic shock, and cardiac arrhythmias, including sinus arrest, AV block, ventricular tachycardia, and ventricular fibrillation during the acute phase. In our case, AV block could be an expression of anteroseptal involvement, documented at CMR. This localization has already been associated with worse clinical presentation and could be a marker of poor prognosis. Diagnosis and treatment of fulminant myocarditis require EMB, to obtain information about the etiology and active viral replication in the heart tissue. In our case, the florid inflammatory state and the absence of viral replication allowed prompt treatment with immunosuppressors, with a quick and full recovery of biventricular function in only two weeks.

PO09: Treatment of Facial Folliculotropic Mycosis Fungoides with High Dose Rate Brachytherapy in Two Fractions

<h3>Purpose</h3> To describe the treatment and outcomes for the treatment of folliculotropic mycosis fungoides (FMF) with high dose rate (HDR) brachytherapy in the facial area with complex topography. <h3>Materials and Methods</h3> A 68-year-old male with past medical history of morbid obesity status post gastric bypass, diabetes mellitus, hypertension, and atrial fibrillation was diagnosed with FMF of the face, scalp, trunk and extremities. Patient was referred to radiation therapy due to severe burning pain and pruritus of facial lesions on the nose, upper lip, and left temple after no response with UVA therapy. Electron beam therapy was initially chosen with a prescription of 3600 cGy in 20 fractions, but the resulting treatment plans were highly non-conformal with large dose heterogeneity and poor target coverage. HDR brachytherapy was pursued as an alternate treatment option with a prescription dose of 800 cGy in 2 fractions. Patient setup for simulation included a custom Freiburg flap applicator on an Aquaplast mask using 18 catheters to cover all lesions. Patient was scanned with pink bolus in the nostrils, a lead shield under the lip, and a bite block. Treatment planning was performed using Oncentra (Elekta, Stockholm, Sweden). HDR treatment was delivered using an Elekta Flexitron remote afterloader unit. Bilateral internal tungsten eye shields (Civco, Orange City, IA) were placed prior to treatment to reduce ocular dose. <h3>Results</h3> The drawn target was 25.2cc along the upper lip, bilateral nose, right medial canthus, and left temple. Achieved target coverage was V90% = 98.6%, D90% = 100.5%, and D95% = 95.9%. Skin V150% was 0.12cc. Without eye shield placement, right and left eye D0.01cc were 117.9% and 78.2%, respectively. Right and left lens doses were 99.1% and 69.4%, respectively. Average fractional delivery time was 603.5 seconds with an air kerma strength of 39.0 mGy*m²/s (apparent activity 9.7 Ci). Patient tolerated treatment without complications. At two week follow up, patient showed grade 1 dermatitis of the treatment area with erythema and mild desquamation. Patient has been asymptomatic six months post treatment. <h3>Conclusions</h3> Low dose HDR brachytherapy can be an effective treatment for facial FMF lesions with complex topography. It allows for suitable target coverage and normal tissue sparing, a shorter treatment course when compared to electron beam radiotherapy, and is associated with minimal adverse effects and rapid clinical response. It also allows sparing total skin electron therapy for the future in case of disease progression as the volume of tissue receiving radiation is very small. Figure 1a: Oncentra treatment plan in axial, sagittal, and coronal planes, with 3D rendering show in bottom right. Target volume in light blue, right eye in green, and left eye in blue. 1b shows wires outlining the target volume (top); pre-mask setup with pink bolus, bite block, gauze in the nostrils, and bilateral eye shields (middle); and final treatment setup with mask (bottom). 1c shows the pre-treatment lesions, and 1d shows the same area four months post treatment.

A CASE OF ANTISYNTHETASE SYNDROME: THE IMPORTANCE OF HISTORY IN DISTINGUISHING ETIOLOGY OF INTERSTITIAL LUNG DISEASE IN A COVID-19 WORLD

A CASE OF ANTISYNTHETASE SYNDROME: THE IMPORTANCE OF HISTORY IN DISTINGUISHING ETIOLOGY OF INTERSTITIAL LUNG DISEASE IN A COVID-19 WORLD

It Melts Like Snow: Steroid Responsiveness of Immunoglobulin G4-Related Disease

Dear Editor, A 35-year-old male presented with insidious onset gradually progressive bilateral painless submandibular swelling, followed by periorbital swelling [Figure 1] for the past 7 years. He had no constitutional or sicca symptoms. He had no history of addiction or autoimmunity in the family. Systemic examination was unremarkable. On evaluation, he had raised inflammatory markers with a negative autoimmune panel. Magnetic resonance imaging orbit showed bilateral orbital extraconal soft-tissue masses with contrast enhancement. Incisional biopsy from the extraconal mass was suggestive of fibrocollagenous stroma with aggregation of lymphocytes, plasma cells, and histiocytes without any necrosis or granuloma. On further evaluation, submandibular gland biopsy showed chronic sialadenitis with immunoglobulin G4 (IgG4)-positive plasma cell >10/hpf and IgG4: IgG ratio >40% [Figure 2] without any major organ involvement on imaging. The diagnosis of IgG4-related disease was kept. He was started on oral steroid 0.5 mg/kg/day and observed a rapid clinical response within 15 days of steroid therapy. Later, he was started on azathioprine and continued with tapering dose of steroid. He was followed up every month for first 3 months and then every 3 monthly upto 16 months without any signs of recurrence. For a long-standing indolent disease of 7 years, drastic steroid response with resolution of clinical symptoms was quite evident in our case.Figure 1: (a) Pretreatment bilateral upper eyelid swelling, (b) pretreatment bilateral submandibular swelling, (c and d) during glucocorticoid therapy (day 15) resolution of orbital and submandibular swelling, respectivelyFigure 2: Salivary gland with seromucinous acini and ducts embedded in mildly fibrotic stroma with numerous lymphoid follicles with germinal centers (a and b: H and E). Clusters of plasma cells are highlighted with CD138 immunohistochemical stain (c). IgG4 positive cells, >10/hpf (d)IgG4-related disease (IgG4-RD) is a chronic, systemic, fibroinflammatory condition with variable organ manifestation. CD4+ T-cells and B-cells are central to the pathogenesis causing organ damage and fibrosis. Marked expansion of IgG4-secreting plasmablast in the blood is usually seen in active and untreated cases.[1] Key to diagnosis is the classical histopathological hallmarks of lymphoplasmacytic infiltrate, storiform fibrosis, and obliterative phlebitis. IgG4 RD usually has a good response to steroids but a variable relapse rate. Factors associated with lesser treatment response and relapse were well analyzed in a Japanese multicenter study. Multivariate analysis from the study revealed that intermediate steroid initial dose (0.4–0.69 mg/day), slow tapering regimen (<0.4 mg/day), and shorter disease duration were associated with a significantly lower rate of disease relapse.[2] The study of isolated IgG4 ophthalmic disease also echoed similar results regarding steroid response and relapse, with more relapse in those with elevated serum IgG4 levels and a shorter duration of initial steroid treatment (<5 months). Low-dose steroid maintenance should be considered to avoid recurrence in patients with elevated serum IgG4 levels.[3] Later on, rituximab therapy showed promising results in inducing remission[4] and steroid-free long-term maintenance.[5] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A Southeast Asian expert consensus on the management of major depressive disorder with suicidal behavior in adults under 65 years of age

BackgroundThe high prevalence of suicidal behavior among individuals with major depressive disorder (MDD) in Southeast Asia (SEA) underscores the need for optimized management to address depressive symptoms, reduce suicide risk and prevent suicide in these individuals. Given the lack of clear guideline recommendations for assessing and managing these patients, regional consensus-based recommendations which take into account diverse local contexts across SEA may provide useful guidance for clinical practice.MethodsA narrative literature review and pre-meeting survey were conducted prior to the consensus meeting of an SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with MDD with suicidal behavior. Utilizing the RAND/UCLA Appropriateness Method, the expert panel developed consensus-based recommendations on the assessment and treatment of adult patients with MDD with suicidal behavior under 65 years.ResultsScreening of adult patients under 65 years with MDD for suicide risk using both a validated assessment tool and clinical interview is recommended. An improved suicide risk stratification – incorporating both severity and temporality, or using a prevention-focused risk formulation – should be considered. For a patient with an MDD episode with low risk of suicide, use of antidepressant monotherapy, and psychotherapy in combination with pharmacological treatment are both recommended approaches. For a patient with an MDD episode with high risk of suicide, or imminent risk of suicide requiring rapid clinical response, or for a patient who had received adequate AD but still reported suicidal behavior, recommended treatment strategies include antidepressant augmentation, combination use of psychotherapy or electroconvulsive therapy with pharmacological treatment, and inpatient care. Suicide-specific psychosocial interventions are important for suicide prevention and should also be part of the management of patients with MDD with suicidal behavior.ConclusionsThere are still unmet needs in the assessment of suicide risk and availability of treatment options that can deliver rapid response in patients with MDD with suicidal behavior. These consensus recommendations on the management of adult patients with MDD with suicidal behavior under 65 years may serve as a useful guidance in diverse clinical practices across the SEA region. Clinical judgment based on careful consideration of individual circumstances of each patient remains key to determining the most appropriate treatment option.

Prevalence of Anti-neural Autoantibodies in a Psychiatric Patient Cohort-Paradigmatic Application of Criteria for Autoimmune-Based Psychiatric Syndromes.

BackgroundAnti-neural autoantibodies associated with psychiatric syndromes is an increasing phenomenon in psychiatry. Our investigation aimed to assess the frequency and type of neural autoantibodies associated with distinct psychiatric syndromes in a mixed cohort of psychiatric patients.MethodsWe recruited 167 patients retrospectively from the Department of Psychiatry and Psychotherapy, University Medical Center Göttingen for this study. Clinical features including the assessment of psychopathology via the Manual for Assessment and Documentation of Psychopathology in Psychiatry (AMDP), neurological examination, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) and electroencephalography (EEG) analysis were done in patients. Serum and or CSF anti- neural autoantibodies were measured in all patients for differential diagnostic reasons.ResultsWe divided patients in three different groups: (1) psychiatric patients with CSF and/or serum autoantibodies [PSYCH-AB+, n = 25 (14.9%)], (2) psychiatric patients with CSF autoantibodies [PSYCH-AB CSF+, n = 13 (7.8%)] and (3) those psychiatric patients without autoantibodies in serum and/or CSF [PSYCH-AB-, n = 131]. The prevalence of serum neural autoantibodies was 14.9% (PSYCH-AB+), whereas 7.2% had CSF autoantibodies (PSYCH-AB CSF+) in our psychiatric cohort. The most prevalent psychiatric diagnoses were neurocognitive disorders (61–67%) and mood disorders (25–36%) in the patients presenting neural autoantibodies (PSYCH-AB+ and PSYCH-AB CSF+). However, psychiatric diagnoses, neurological deficits, and laboratory results from CSF, EEG or MRI did not differ between the three groups. To evaluate the relevance of neural autoantibody findings, we applied recent criteria for possible, probable, or definitive autoimmune based psychiatric syndromes in an paradigmatic patient with delirium and in the PSYCH-AB+ cohort. Applying criteria for any autoimmune-based psychiatric syndromes, we detected a probable autoimmune-based psychiatric syndrome in 13 of 167 patients (7.8%) and a definitive autoimmune-based psychiatric syndrome in 11 of 167 patients (6.6%).ConclusionsNeural autoantibodies were detected mainly in patients presenting neurocognitive and mood disorders in our psychiatric cohort. The phenotypical appearance of psychiatric syndromes in conjunction with neural autoantibodies did not differ from those without neural autoantibodies. More research is therefore warranted to optimize biomarker research to help clinicians differentiate patients with potential neural autoantibodies when a rapid clinical response is required as in delirium states.

Due anni di MIS-C: peculiarità cliniche e orizzonti terapeutici

Introduction - MIS-C is the most relevant complication of SARS-CoV-2 infection and has an incidence of 1 case / 2,200 children and adolescents with previous infection. The clinical picture is characterized by a multiorgan involvement and an insufficiently known response to therapy. Objectives - Retrospective analysis carried out in the Paediatric Department of the Ravenna Hospital from April 2020 to March 2022 of the cases admitted with MIS-C, with description of the presentation characteristics, the differences with respect to Kawasaki disease and the therapeutic strategies adopted also with regard to the clinical response. Results - Thirteen cases diagnosed with MIS-C with an average age of 6 years and four months were hospitalized, 4 cases were of Italian origin, 6 of Balkan and 3 of African. All the cases presented with fever&gt; 39 ° C with severe malaise / irritability, associated with skin rash in 9 cases, conjunctivitis in 7 and cheilitis in 5. The most prominent manifestations of organ involvement were abdominal pain / diarrhoea (N = 9), myocardial dysfunction in the absence of coronary involvement (N = 5), presence of pulmonary thickening (N = 5), painful laterocervical lymphadenitis with reduced neck motility (N = 5), subnephrotic proteinuria (N = 7) and hypertransaminasaemia (N = 8). Two cases with “encephalitic-like” psychomotor slowing, one with important ascites and one with oedema of the para/retropharyngeal tissues were clinically relevant for the severity of the onset. Twelve cases were treated with IVIG and methylprednisolone (2 mg /kg), 4 of them were found to be non-responders and required the use of steroid boluses (4 cases) and anakinra (4 cases), in three of the latter in association with steroid boluses, with rapid and decisive clinical response. Conclusions - The serious clinical manifestations that characterize MIS-C do not concern only cardiac involvement. Therapy with an IL-1 inhibitor, anakinra, must also be envisaged as a possible first-line treatment in case of a particularly severe clinical picture at the onset.

Pressure pain thresholds in a real-world chiropractic setting: topography, changes after treatment, and clinical relevance?

BackgroundChanges in pain sensitivity are a commonly suggested mechanism for the clinical effect of spinal manipulative therapy (SMT). Most research has examined pressure pain thresholds (PPT) and has primarily been conducted in controlled experimental setups and on asymptomatic populations. Many important factors are likely to differ between research and clinical settings, which may affect PPT changes following SMT. Therefore, we planned to investigate PPT before and after clinical chiropractic care and investigate relationships with various potentially clinically-relevant factors.MethodsWe recruited participants from four Danish chiropractic clinics between May and August 2021. A total of 129 participants (72% of the invited) were included. We measured PPT at eight pre-determined test sites (six spinal and two extra-spinal) immediately before (pre-session) and immediately after (post-session) the chiropractic consultation.We used regression analyses to investigate PPT changes, including the following factors: (i) vertebral distance to the nearest SMT site, (ii) rapid clinical response, (iii) baseline PPT, (iv) number of SMTs performed, (v) at the region of clinical pain compared to other regions, and (vi) if other non-SMT treatment was provided. We also performed topographic mapping of pre-session PPTs.ResultsAfter the consultation, there was a non-significant mean increase in PPT of 0.14 kg (95% CIs = − 0.01 to 0.29 kg). No significant associations were found with the distance between the PPT test site and nearest SMT site, the clinical response of participants to treatment, the pre-session PPT, the total number of SMTs performed, or the region/s of clinical pain. A small increase was observed if myofascial treatment was also provided. Topographic mapping found greater pre-session PPTs in a caudal direction, not affected by the region/s of clinical pain.ConclusionsThis study of real-world chiropractic patients failed to demonstrate a substantial local or generalized increase in PPT following a clinical encounter that included SMT. This runs counter to prior laboratory research and questions the generalizability of highly experimental setups investigating the effect of SMT on PPT to clinical practice.

Long-Term Follow-Up and Immunomonitoring of Relapsing Type 1 Autoimmune Pancreatitis Treated With Rituximab.

To evaluate the efficacy and safety of rituximab in relapsing type 1 autoimmune pancreatitis especially the long-term clinical and immunologic impacts. All consecutive patients with type 1 autoimmune pancreatitis were retrospectively included. The rituximab protocol was induction therapy of 375 mg·m -2 intravenous weekly for 4 weeks, followed by 500 mg intravenous every 6 months for 2 years. The follow-up included clinical examinations, biological tests, positron emission tomography scan, and immunomonitoring of lymphocyte CD 19+. Among the 43 patients included, 15 received rituximab induction therapy, followed by maintenance in 10 cases because of 1 or more relapses after steroids (whether or not followed by immunosuppressants) and multiple organ involvement. All patients had a clinical, biological and morphological response, a deep and persistent drop in serum immunoglobulin G4 levels, an extinction of both pancreatic and extra pancreatic hypermetabolic positron emission tomography scan signals, and a depletion of B lymphocyte CD19+. No relapse occurred during the follow-up (62.8 ± standard error of the mean of 11.1 months). Rituximab is an effective treatment for type 1 autoimmune pancreatitis that provides a rapid strong clinical, biological, and morphological response, which persists after discontinuation without any safety issues.

Hemichorea as initial presentation of newly diagnosed diabetes and acute lacunar stroke

Hemichorea is one of the spectrums of involuntary, continuous, non-purposeful movement of one side of the body, a choreiform disorder. Hemichorea causes vary and include various inherited or acquired systemic conditions. There might be overlapping pathophysiology where the synergistic effects of uncontrolled hyperglycemia and vascular insufficiency cause an incomplete transient dysfunction of the striatum, leading to hemichorea. We herein describe a patient who presented with hemichorea triggered by hyperglycemia and was incidentally found to have an acute lacunar stroke. She was initiated on insulin with good glycemic control. Secondary stroke prevention therapy with aspirin and statin was also started. Her symptoms improved inpatient after stable glycemic control was achieved. After 3 months, her symptoms had completely resolved. Hemichorea is an unusual initial presentation for newly diagnosed diabetes mellitus or stroke. Hence, recognizing and diagnosing this uncommon disease entity is pertinent to make a timely and accurate diagnosis, which can lead to a rapid clinical response.

Abstract #1165468: Stalk Effect: Cushing’s Disease Mistaken for Prolactinoma

The diagnostic workup for hypercortisolism is not infrequent in clinical practice. Common findings of high cortisol are weight gain, facial plethora, and menstrual irregularity. Here we discuss a distinct presentation of amenorrhea and galactorrhea as an unexpected exhibition of Cushing’s disease. A 35-year-old woman with a history of obesity presented with the chief complaint of infertility. Six months prior, she began to experience amenorrhea, galactorrhea, headaches, excessive sweating, and weight gain. Serum prolactin (PRL) level was found to be mildly elevated at 35.3 ng/mL. Magnetic resonance imaging (MRI) of the brain demonstrated a 11 mm x 9.8 mm x 9.6 mm pituitary macroadenoma. She was started on oral cabergoline 0.5 milligrams twice weekly for prolactinoma treatment, with resolution of all symptoms and return to normal PRL range. Tumor size on repeat MRI was stable. Six months later, she conceived. Cabergoline was stopped. She delivered a healthy infant but developed recurrence of her symptoms, now with diplopia. PRL was elevated at 61.9 ng/mL. Cabergoline was reinitiated. Further labs demonstrated elevated plasma adrenocorticotropic hormone (ACTH) of 121 pg/ml, elevated morning salivary cortisol of 0.217 ug/dL and elevated urinary free cortisol of 142 ug/24 hour. Overnight dexamethasone test showed unsuppressed cortisol. Cushing’s disease was diagnosed. Tumor size was 13 mm x 17 mm x 17 mm prior to surgical resection. Tumor pathology showed corticotroph adenoma. PRL highlighted in just a few scattered tumor cells. Her elevated prolactin levels were ultimately suspected to be due to stalk effect. Approximately 40% of all pituitary adenomas are prolactinomas. Clinical signs and symptoms of hyperprolactinemia include infertility, amenorrhea, and galactorrhea. Mild elevations of prolactin may cause infertility and can be consistent with prolactinoma. Amenorrhea associated with galactorrhea strongly suggests hyperprolactinemia. However, clinicians must note that in the presence of sellar mass and mild hyperprolactinemia, a non-prolactin-secreting mass must first be diagnostically ruled out. Cushing’s disease may present similarly with menstrual irregularities, hyperprolactinemia, and galactorrhea due to stalk effect. This patient demonstrated initial diagnostic uncertainty due to her incomplete workup and rapid clinical response to cabergoline. Her elevations in prolactin and response to cabergoline at the time of her original presentation may substantiate the proposed off-label use of dopamine agonists in non-prolactinoma pituitary tumors.

Çoklu İlaca Dirençli Gram-negatif Bakteriyel Enfeksiyonların Tedavisinde Yükleme Dozlu veya Yüklemesiz Kolistin Tedavisinin Etkinliğinin Değerlendirilmesi

Aim: Colistin (Col) is an agent used in the treatment of multidrug-resistant gram-negative (MDRGN) bacterial infections. This drug has been administered with a loading dose in recent years to provide rapid clinical response and therapeutic blood levels. In our study, we aimed to evaluate whether there is a relationship between the efficacy of the loading dose of Col treatment, mortality, microbiological clearance during treatment, nephrotoxicity, and neurotoxicity side effects for the treatment of MDRGN bacterial infections. Material method: In this retrospective study, which included a control group, 6-years data was analyzed. Totally, 323 patients who received Col treatment with or without loading dose (LD) were included in the study. Patients were divided into two groups; I: without Col-LD regimen (those who were hospitalized in 2011-2014), II: with Col-LD regimen (those who were hospitalized in 2015-2017). Demographic characteristics such as age, gender, microbiological cultures, laboratory results, side effects, and mortality of the patients were evaluated. Results: A statistically significant relationship was found between with Col-LD regimen and nephrotoxicity. However, it was determined that there was no statistically significant relationship between microbiological clearance without a Col-LD regimen. Nephrotoxicity was found to be decreased with the Col-LD regimen. Neurotoxicity was observed more frequently (3.7%) in with Col-LD regimen. Initial and final C-reactive protein (CRP) and procalcitonin (PCT) levels were statistically significantly lower in with Col-LD regimen. Conclusion: It was found that with Col-LD regimen had a statistically significant effect on nephrotoxicity, neurotoxicity, and treatment outcome, but had no effect on microbiological clearance. In addition, with Col-LD regimen was effective in decreasing CRP and PCT values.

EFFICACY OF LOW DOSE NALTREXONE IN PATIENTS WITH CROHN’S COLITIS AND ILEITIS

Abstract In a Phase 2 placebo-controlled trial, low dose naltrexone (LDN) improved inflammation of the gastrointestinal mucosa and improved clinical activity scores in patients with mild to moderate Crohn’s disease (CD). We present two patients with symptomatic CD with a rapid clinical and endoscopic response to LDN: 1) Crohn’s colitis with prolonged maintenance to LDN which had failed mesalamine with immunomodulator therapy; and 2) Crohn’s ileitis with prolonged remission with addition of LDN to biologic and immunomodulator therapy. CASE 1: A 43-year-old male with a 23-year history of Crohn’s colitis of mild-to-moderate severity was previously treated with 150 mg mercaptopurine and mesalamine. Despite this treatment he had left-sided abdominal cramping, urgency, and 8-12 loose bowel movements with bleeding. Colonoscopy showed severe rectal ulcerations and normal ileum (Figure 1A). He started 1 mg oral naltrexone daily which was increased to 4 mg daily over 1 mo and a tapering course of budesonide. Mesalamine was continued. Six mo later, he stated he had 2 to 3 semi-formed bowel movements daily without bleeding or urgency. He was maintained on mesalamine and LDN 4.5 mg daily for 3 years. Colonoscopy showed dramatic improvement of rectal ulcerations and 3 small erosions in the proximal ascending colon which were not present on the previous colonoscopy (Figure 1B). At the time of this colonoscopy he was doing well clinically with a plan to augment LDN therapy with a probiotic and an anti-inflammatory diet. This case demonstrates favorable clinical and endoscopic response to an LDN-based regimen that was rapid and durable, with a short exposure to steroid. CASE 2: A 42-year-old female with a history of severe CD of the colon and ileum starting at age 27. She required total colectomy and end ileostomy at age 36. Three years after surgery she developed recurrent ileal ulcerations and strictures leading to further ileal resection. Later that year, ileoscopy demonstrated ileal ulcers (Figure 2A) and she was started on infliximab and mercaptopurine. She was stable for 3 years but then developed higher ileostomy output and fatigue. Methotrexate was substituted for mercaptopurine which helped reduce symptoms for 2 years. With increasing ostomy output, infliximab dosing interval was reduced from 8 weeks to 5 weeks which led to less output and less fatigue. After a year, symptoms returned, and naltrexone was added with 1 mg increasing to 4.5 mg over 1 month. Within 4 months, her symptoms were in remission and ileoscopy showed flat scars where ulcers had been seen in the past (Figure 2B). Her disease remained in endoscopic remission for 3 years documented by two more ileoscopies. The patient maintained clinical response to the combination of infliximab (6 week intervals), methotrexate, and LDN. Owing to a change in insurance she was lost to follow up at this point. Figure 1. Rectal images before starting LDN for CD (A) and 3 years of maintenance therapy with LDN (B) Figure 2. Ileal ulcers seen after the second surgery (A) and scar tissue seen at the ulcer sites at the time the patient with on infliximab, methotrexate, and LDN (B)

EFFICACY OF LOW DOSE NALTREXONE IN PATIENTS WITH CROHN’S COLITIS AND ILEITIS

In a Phase 2 placebo-controlled trial, low dose naltrexone (LDN) improved inflammation of the gastrointestinal mucosa and improved clinical activity scores in patients with mild to moderate Crohn’s disease (CD). We present two patients with symptomatic CD with a rapid clinical and endoscopic response to LDN: 1) Crohn’s colitis with prolonged maintenance to LDN which had failed mesalamine with immunomodulator therapy; and 2) Crohn’s ileitis with prolonged remission with addition of LDN to biologic and immunomodulator therapy.

Эффективность и безопасность устекинумаба у пациентов с воспалительными заболеваниями кишечника в реальной клинической практике

Relevance. Therapy of Crohn's disease (CD) and ulcerative colitis (UC) still remains an urgent problem in modern gastroenterology. Unfortunately, currently there are not enough medications to achieve clinical, endoscopic, histological remission of inflammatory bowel diseases (IBD). The aim is to retrospectively evaluate the efficacy and tolerability of ustekinumab (UST) therapy in patients with moderate and severe CD and UC in real clinical practice. Material and methods. To assess the effectiveness and safety of UST, we included in the study 54 patients with IBD (42 – BC, 12 – UC) who received at least one UST injection from December 2019 to November 2021 at the A.S. Loginov Moscow Clinical Scientific and Practical Center (MCSC). The average age is 35.5 years. Anamnesis of the disease – from 1 to 26 years – 9.5 (95% CI 7.9–11.1). The vast majority (92.6%) of them received previous therapy with genetically engineered biological drugs (GIBD). Results. A rapid clinical response on the third day of treatment, characterized by a decrease in stool frequency, a decrease in the intensity of abdominal pain syndrome and an improvement in general well-being, was observed in 46 (85.2%) of 54 patients. Four months after the first oral injection, 19 patients (CD – 16, UC – 3) underwent a full examination at the A.S. Loginov MCSC. Subsequently, therapy was canceled for three of them for reasons: primary inefficiency, secondary inefficiency, unknown. A decrease in disease activity was noted in all patients during therapy: the initial values of the indices of all patients were from 8 to 11 points, after four months only two patients with CD had a Best index of 9, the rest had an interval from 2 to 5, in three patients with UC the Mayo index was 4 points. The mean baseline value of the CDAI decreased after four months compared to the baseline from 9.31 (95% CI 8.52–10.11) points to 3.81 (95% CI 2.66–4.97) (p &lt; 0.001), the Mayo index – from 9.33 (95% CI 3.6–15.07) to 3.33 (95% CI 0.46–6.2) points (p = 0.11), respectively. In no case has the appearance of adverse events that could cause the withdrawal of the drug been noted. Conclusion. Clinical observation of a group of patients with CD and UC, as well as previous multicenter studies, demonstrated the high effectiveness of UST in induction and maintenance therapy of a cohort of patients with severe and moderate forms of CD and UC resistant to basic drugs and GIBP

Тактика ведения пациентов с язвенным колитом, не ответивших на лечение анти-ФНО

Effective methods of treating UC patients is one of the most important problems. The inclusion of biological drugs in clinical practice leads to an improvement in the treatment of moderate and severe UC, but from 10 to 20% of patients lose their response within a year, which leads to the need to optimize the dose or switch to another drug. The use of janus kinase inhibitors – a new class of targeted synthetic drugs for the treatment of active ulcerative colitis – allows for a rapid clinical response when switching from TNF-α inhibitors. Pronounced clinical efficacy is usually observed 2-8 weeks after the start of treatment. A clinical case of a patient with ulcerative colitis who did not respond to treatment with anti-TNF is presented. Modern approaches to the diagnosis of ulcerative colitis and treatment tactics are reflected, as well as therapeutic possibilities for overcoming the secondary inefficiency of TNF inhibitors by using janus kinase inhibitors

Rilonacept for the treatment of recurrent pericarditis

ABSTRACT Introduction Recurrent pericarditis (RP) is a debilitating disease that has an underlying autoinflammatory pathophysiology mediated by cytokine interleukin (IL)-1. Rilonacept, a recombinant dimeric fusion protein that blocks IL-1α and IL-1β signaling has emerged as a valuable therapeutic option of RP. Rilonacept has been evaluated in Phase 2 and 3 clinical trials and was recently approved for RP treatment. Areas covered This article reviews available clinical trials assessing the efficacy and safety of rilonacept for the treatment of RP. Expert opinion Findings from the Rhapsody study) trial suggest that rilonacept represents a promising new therapy for those patients with colchicine resistant or glucocorticoid-dependent disease. Treatment leads to rapid clinical response, with a median resolution of symptoms in 5 days, normalization of C-reactive protein (CRP) in a median of 7 days, and successful weaning from glucocorticoids. This novel therapy also reduces recurrence rates compared with placebo. Rilonacept has also demonstrated a good safety profile, with the most common adverse events including injection-site reactions and upper respiratory tract infections. This anti-IL 1 agent has emerged as an efficacious treatment for RP, with potential use for glucocorticoid-free regimens and as monotherapy. Future trials are needed to explore these treatment options and to clarify the appropriate therapy duration.