Triple Regimen Research Articles

Managemnet of Fournier’s Gangrene at Department of Urology Chandka Medical College Hospital

Aims and object: To assess the aetiology and management of Fournier’s gangrene. Methodology: We examined 30 paients retrospectivdely, during the period from 2015 to 2020, the patients from the Urology department of CMC Hospital at SMBB Medical University Larkana. All the related data were taken as well as demographic details, history and risk factor from the patients regarding illness. Routine investigation carried out including Blood CP ESR, Urine Dr, Blood sugar, Renal profile and pus culture sensitivity. 20 patients under gone for surgical debridement, 5 patients require skin grafting and 4 patients requires testes burrial after recovery under aseptic measures. Result: 30 male patients with mean age 20±10.5 year. Majority (80%) of patient presenting with necrotising infection on scrotum,perineum and hypogatric area. Basic laboratory investigations including Blood CBC showed mean WBC 15000/cmm3, mean Hb was 8.5 gms, Urine analysis showed pyuria and haematuria, pus culture and sensitivity positive in 90% cases and most prevalent organism was E.Coli, Mean Blood urea was 35mg and serum creatinine was 1.9mg. Commonest causes of fourneir gangreen was trauma, UTI, urethral stricture, indewelling catheter and perianal abcess and D.M was commonest comorbidity). All patients treated by surgical debridement while 5 patients requires skin grafting and 4 patients requires testes burrial after recovery under aseptic measures with with triple regimen antibiotics. Conclusion: Surgical debridment of necrotic tissues and triple regimen antibiotic are the main stay for primary management of Fournier’s gangrene (FG) to decrease the morbidity and mortality keywords: Fournier’s Gangrene, surgical debriment, and triple regimen antibiotics.

Enhancing Patient Outcomes in Aesthetic Breast Implant Procedures Using Proven Antimicrobial Breast Pocket Irrigations: A 20-Year Follow-up.

Capsular contracture (CC) remains the most common complication of implant-based aesthetic and reconstructive breast surgery. With subclinical infection proven to be the primary etiology, antimicrobial breast pocket irrigation has been recommended as the key step to reduce CC but has not been universally adopted. The purpose of this study was to review the rates of CC observed when applying proven antimicrobial breast pocket irrigations. Data from patients undergoing cosmetic breast augmentation were recorded prospectively from 1997 to 2017. The irrigation was performed with either a Betadine-containing (50% Betadine or "Betadine triple") or a non-Betadine triple antibiotic regimen. The database was assessed to determine the type of implant used, the incidence of CC, and possible contributing factors. The degree of CC was recorded according to the Baker classification. A 20-year prospective data collection yielded 2088 patients with 4176 implants; of these patients, 826 had textured implants and 1262 had smooth implants. The incidence of Grade III/IV CC was found to be 0.57% in all patients undergoing primary breast augmentation (1.21% in textured implants and 0.16% in smooth implants). This study constitutes the largest and longest review of CC in a controlled, single-surgeon setting. The incidence of CC is low and reinforces the efficacy/utility of antimicrobial breast pocket irrigation. Both the Betadine and non-Betadine antibiotic regimens were found to be effective, with the Betadine regimen being preferred. Universal adoption of Betadine-containing antimicrobial breast pocket irrigation is recommended to reduce CC and other device-associated infections.

Comparison of eradication rates of moxifloxacin-rifabutin triple therapy and bismuth quadruple therapy as second-line regimens in patients with peptic ulcers.

BackgroundBismuth quadruple (BQ) therapy is known to have poor patient compliance and a complex dosing method, and no appropriate third‐line regimen exists if second‐line BQ therapy fails. In Korea, some alternative regimens have shown unsatisfactory eradication rates. Therefore, we investigated the success rates of the second‐line moxifloxacin–rifabutin triple (MRT) regimen and compared it with BQ regimen in subgroup analysis of peptic ulcer patients.Materials and MethodsThis study was a retrospective study of 71 patients who underwent a second‐line MRT for Helicobacter pylori after failing to clarithromycin triple regimen. To compare the eradication rate in gastric ulcer patients, 51 patients in the MRT group and 132 patients in BQ group were included. After age and sex propensity matching, 45 patients were included in each group (the alpha value and power were set at 0.05% and 77%, respectively).ResultsThe eradication rate in the MRT group was 69.0% (49/71) in the intention‐to‐treat (ITT) analysis and 77.8% (49/63) in the per‐protocol (PP) analysis. These were significantly lower than the eradication rate in the BQ group (82.5%, p = 0.019 in the ITT analysis; 89.3%, p = 0.022 in the PP analysis). In subgroup analysis of peptic ulcer patients, the success rate of BQ group was significantly higher than that of MRT group in both ITT and PP populations (81.8% (108/132) vs. 60.8% (31/51) in the ITT populations, p = 0.004; and 90.0% (108/120) vs. 72.1% (31/43) in the PP populations, p = 0.010). Among the 14 patients with MRT therapy failure, 10 were eradicated with BQ as the third‐line regimen. The eradication rate of the third‐line BQ after the second‐line MRT failure was 90.0% (9/10).ConclusionSecond‐line MRT therapy was not as effective as BQ therapy, so it should be considered for limited use only when BQ is not available.

Third dose of the BNT162b2 vaccine in cardiothoracic transplant recipients: predictive factors for humoral response.

BackgroundWe report the results of a prospective study on the immunogenicity of a 3rd dose of BNT162b2 in thoracic organ recipients with no or minimal response following a two-dose BNT162b2 vaccination scheme.MethodsA total of 243 transplant recipients received a homologue 3rd dose. Anti-SARS-CoV2-immunoglobulins (IgGs) were monitored immediately before (T1), 4 weeks (T2) as well as 2 and 4 months after the 3rd dose. Neutralizing antibody capacity (NAC) was determined at T2. To reveal predictors for detectable humoral response, patients were divided into a positive response group (n = 129) based on the combined criteria of IgGs and NAC above the defined cut-offs at T2—and a group with negative response (n = 114), with both, IgGs and NAC beyond the cut-offs.ResultsThe 3rd dose induced a positive humoral response in 53% of patients at T2, 47% were still non-responsive. Sero-positivity was significantly stronger in patients who presented with weak, but detectable IgGs already prior to the booster (T1), when compared to those with no detectable response at T1. Multivariable analysis identified age > 55 years, a period since transplantation < 2 years, a reduced glomerular filtration rate, a triple immunosuppressive regimen, and the use of tacrolimus and of mycophenolate as independent risk factors for lack of humoral response.ConclusionsOur data indicate that a lack of immunogenicity is linked to the type and extent of maintenance immunosuppression. The necessity of the cumulative immunosuppressive regimen might individually be questioned and possibly be reduced to enhance the chance of an immune response following an additional booster dose.

Efficacy of triple dose albendazole treatment for soil-transmitted helminth infections.

In Malaysia, soil-transmitted helminth (STH) infections still persist among indigenous communities. In the past, local studies have focused mostly on epidemiologic aspects of STH infections with a scarcity of information on the efficacy of deworming treatment. The present study consisted of 2 phases: a cross-sectional phase on current epidemiological status and risk factors of STH infections and a longitudinal study over 6 weeks on triple dose albendazole efficacy against STH infections. A total of 253 participants were recruited at baseline and a pre-tested questionnaire was administered to obtain information on socio-demographics, environmental and behavioural risk factors. Stool samples were evaluated using a modified Kato-Katz technique. Cure rate (CR) and egg reduction rate (ERR) were assessed at 3 weeks following a 3-day course of 400mg albendazole treatment and infection status were observed again at 6 weeks. Baseline positivity of trichuriasis, ascariasis and hookworm infections were 56.1%, 11.9% and 20.2%, respectively. Multivariate analysis showed age below 18 years old (P = 0.004), without latrine in house (P = 0.042) and indiscriminate defecation (P = 0.032) were associated with STH infections. In the longitudinal study (N = 89), CR for trichuriasis was 64.6%, while CR of 100% was observed for both ascariasis and hookworm. ERR was above 90% for all three STH species. A rapid increased of Trichuris trichiura egg output was observed at 6 weeks. In conclusion, STH infections are highly prevalent among indigenous communities. Children and teenagers, poor sanitation and hygiene behaviour were determinants for STH infections. Triple dose albendazole is found to be efficacious against Ascaris lumbricoides and hookworm infections but has moderate curative effect with high ERR against T. trichiura. Although triple dose albendazole regimen has logistic challenges and may not be a routine option, consideration of this treatment regime may still be necessary in selective communities to reduce high intensity of T. trichiura infection.

Fatal Case of EBV-negative Posttransplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis in an Adult Kidney Transplant Recipient.

Fatal Case of EBV-negative Posttransplant Lymphoproliferative Disorder With Hemophagocytic Lymphohistiocytosis in an Adult Kidney Transplant Recipient.

Pomalidomide in relapsed and refractory multiple myeloma: multicenter retrospective study

Background. The treatment options for patients with multiple myeloma who refractory to previous bortezomib and lenalidomide therapy are limited. Pomalidomide is ап immunomodulatory agent that was registered for the treatment of patients with double refractory multiple myeloma.Aim. To evaluate efficacy, safety and optimal course of the therapy with pomalidomide in routine practice in patients with double refractory multiple myeloma.Materials and methods. Overall, 71 patients with double refractory multiple myeloma were included in the retrospective analysis. There were 36 males and 35 females. The median age was 61 years (range 35-79). According to Durie-Salmon staging system, there were 53 (79.1 %) patients in stage III, 13 (19.4 %) - stage II, and 1 (1.5 %) - stage I.The stage was unknown in 4 patients. Kidney impairment at the onset was in 10 (15 %) patients, the normal function was in 57 (85 %) patients and 4 patients had no data. Most patients (n = 68, 95.8 %) received pomalidomide in one therapy line, in 3 (4.2 %) patients - drug was given in two lines, totally 74 episodes of use. Median number of drugs prescribed prior to pomalidomide were 4 (2-9) drugs, including target ones - 2 (2-5). In the first remission 31 (43.6 %) patients received high-dose therapy with autologous stem cell transplantation. pomalidomide was administered in combination with low doses of dexamethasone (PomDex, n = 44; 59.4 %) and as a part of triple regimens (n = 30; 40.6 %). previously exposed (n = 22; 73.3 %) and new drugs (n = 8; 26.7 %) were used in the combination treatment. In 44 (61.9 %) patients pomalidomide was administered more than 3 years after the onset of the disease, median 63.5 (37-184) months. In 27 (38.1 %) patients it was given within less than 3 years after the onset, median 21 (6-36) months. The primary endpoint was progression-free survival. Secondary endpoints - pomalidomide tolerability, response rate and optimal third drug in the triple regimen. The dependence of progression-free survival, frequency of response and adverse events from the pretreatment, the choice of the third drug, gender, age, immunochemical variant, stage according to the International Staging System and to Durie-Salmon classification was studied.Results. The median time from the diagnosis to the start of pomalidomide therapy was 44.5 (6-184) months. The median of cycles with pomalidomide was 3 (1-30). The response was achieved in 52 (70 %) patients. The median progression-free survival was 4 (1-30) months, overall survival - 6 (0.5-42) months. Adverse effects were noted in 34 (46.5 %) patients. The most frequent adverse events were neutropenia grade III-IV (n = 14; 41.3 %), infection (n = 7; 20.7 %) and fatigue with limitation of daily activity (n = 6; 20.6 %). The rate of adverse events was higher in patients with triplets than doublets regimens of therapy: 43.3 % (n = 13) and 27.2 % (n = 12) respectively (p = 0.008). There were no statistically significant differences in progression-free survival between pomalidomide treatment options (two- or three-component regimen).Conclusion. Compared to the three-component therapy consisting of drugs to which refractoriness was previously diagnosed the PomDex scheme is less toxic and equally effective. Therapy with pomalidomide is effective in the majority of patients with double refractory multiple myeloma even in heavily pretreated. The toxicity is acceptable.

Raoultella Species Associated Sepsis in Children: A Case Series at a Tertiary Hospital, Karachi

To determine the clinical outcome and management options of gram-negative Raoultella species reported at a tertiary care pediatric Hospital in Karachi. Descriptive study. Pediatric and child Health department of The Aga Khan University Hospital from January 2017 to June 2020. A retrospective chart review was done. Data was extracted for 20 patients with culture-positive Raoultella species. Study variables included demographic features, infection site, antibiotic sensitivities, Hospital duration, clinical outcome, and management options. Data were summarised using descriptive statistics and Kaplan-Meier plots using SPSS version 22. A total of twenty-three site cultures positive with Raoultella species were isolated among 20 children with a wide array of clinical symptoms and disease severity. Predominantly the organism was isolated in blood with 12 positive cultures (60%). Eleven (55%) of the patients were females having a median age of 9.5 months. Multidrug-resistant (MDR) and extensively drug-resistant species (XDR) were isolated from eleven (47.8%) and ten (43.5%) culture sites respectively. Combination therapy of colistin or fosfomycin with carbapenem and tigecycline (triple regimen) was used in seven (35%) patients with severe sepsis. Microbiological clearance (sterility) was achieved in twelve (60%) children. Eight children (40%) died of MDR/XDR Raoultella associated sepsis. Highly resistant Raoultella species were associated with high mortality among reported cases, with a limited choice of antibiotics and combination therapy. The management of Raoultella species is required with a multi-specialty approach. Furthermore, strict antimicrobial stewardship measures are required to control an outbreak of MDR and XDR infections in Pakistan. Raoultella species, Enterobacteriaceae, Children, Multidrug-resistant, Antimicrobial resistance.

Role of Probiotics in the Management of Helicobacter pylori.

The global prevalence of Helicobacter pylori (H. pylori) is estimated to be around 4.4 billion, with the majority of individuals affected in developing countries. Chronic infection of the gram-negative bacterium results in several gastrointestinal pathologies such as chronic gastritis, peptic ulcer, and cancer. Probiotics compete directly with H. pylori and help restore the gut microbial environment; these living microorganisms are comparatively more effective than the standard triple antibiotic regimen in the management of symptoms related to the pathogenic bacteria. The need for alternative therapy is better explained by the increasing rate of antibiotic resistance and the lowering of patient compliance to the standard treatment. Adjuvant administration of probiotics to H. pylori eradication therapy is associated with a higher H. pylori eradication rate, decreased diarrhea-related treatment, less common self-reported side effects, and higher treatment compliance. Therefore, with the ongoing and future resistance to antibiotics, this systematic review aims to investigate the use and efficacy of probiotics when used alone or in conjunction with the current guideline treatment.A literature search was conducted using Pubmed, MEDLINE, and Cochrane for peer-reviewed articles published between January 1, 2016 and April 2022. MeSH terms used were: “H. pylori,” “H. pylori and probiotics,” “Probiotics,” “H. pylori treatment,” “Mechanism of Action” with subheadings as “clinical manifestations,” “treatment,” and “diagnosis.” All literature reviews, original papers, and case reports were included. This search strategy aimed to find literature that could describe the transmission and mechanism of action of H. pylori, the current treatment guidelines, and the efficacy of probiotics in eradicating H. pylori.

Abstract 3448: The IV STING agonist, TAK-676, enhances immune-mediated anti-tumor activity of radiation in syngeneic mouse models

Abstract Robust interferon (IFN) signaling is integral for productive immune-mediated anti-tumor responses; however, impaired IFN signaling has been linked to checkpoint inhibitor (CPI) resistance. The cyclic GMP-AMP Synthase (cGAS)-STimulator of InterferoN Genes (STING) pathway is an essential regulator of IFN signaling in response to aberrant cytosolic DNA, including from tumors, and has emerged as an attractive therapeutic target. TAK-676 is a systemically delivered novel synthetic STING agonist that binds to and activates STING along with downstream IFN signaling, which is currently being evaluated in a Phase 1 dose escalation study of patients with advanced tumors (NCT04420884). In addition, focal radiation treatment of tumors leads to cell death coupled with innate cell activation and antigen presentation, suggesting that combining STING activation with radiotherapy (+/- anti-PD1) could lead to improved tumor control. The combination of TAK-676 with radiation +/- anti-PD1 was explored in immunocompetent EMT6 tumor-bearing BALB/c mice. Fractionated focal radiation (8Gy X 3) followed by TAK-676 (1 mg/kg dosed Q3D X 3) resulted in complete regression (CR) of tumors in 6/8 mice, whereas no CRs were detected in groups treated with radiation alone or with TAK-676 as a single agent. These observations suggest that addition of TAK-676 to a radiation regimen leads to enhanced tumor growth control compared to either treatment alone. In contrast, adding anti-PD1 to TAK-676 + fractionated radiation did not further increase tumor growth inhibition in this anti-PD1 resistant tumor model, with 5/8 CRs detected. Rechallenge of mice achieving CRs with EMT6 tumors resulted in rejection of the tumors in 3/5 and 4/5 mice from the double and triple combinations regimens, respectively, suggesting establishment of immunologic memory following primary challenge and treatment. Pharmacodynamic studies found both TAK-676 (1mg/kg) and fractionated radiation (8Gy X 3) monotherapy led to increased T cell accumulation and activation in the lymph nodes. However, only TAK-676 with fractionated radiation enhanced local IFN-γ production within the tumor, suggesting an enhanced adaptive immune response to this combination that drives the increase in observed efficacy. These studies support the evaluation of TAK-676 in combination with pembrolizumab following fractionated stereotactic body radiation therapy (SBRT) in a dose escalation clinical trial in patients with select advanced tumors (NCT04879849). Citation Format: Vicky A. Appleman, Allison J. Berger, Emily R. Roberts, Angel E. Maldonado-Lopez, Michelle L. Ganno, Camilla I. Christensen, Tiquella Hatten, Yosuke Sato, Michael H. Shaw, Karim S. Malek, Neil B. Lineberry, Adnan O. Abu-Yousif, Richard C. Gregory. The IV STING agonist, TAK-676, enhances immune-mediated anti-tumor activity of radiation in syngeneic mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3448.

Multiple-day administration of fosaprepitant combined with tropisetron and olanzapine improves the prevention of nausea and vomiting in patients receiving chemotherapy prior to autologous hematopoietic stem cell transplant: a retrospective study

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase.

Interim analysis from a phase II study of olaparib maintenance with pembrolizumab and bevacizumab in BRCA non-mutated patients with platinum-sensitive recurrent ovarian cancer: APGOT-ov4/ OPEB-01.

e17579 Background: The optimal treatment of BRCA wild-type patients with platinum-sensitive recurrent (PSR) ovarian cancer remains controversial. This single arm phase 2 study (OPEB-01) evaluated a triple combination regimen with olaparib, bevacizumab, and pembrolizumab as 2nd-line maintenance treatment in BRCA non-mutated, PSR ovarian cancer. Methods: Women with PSR ovarian cancer who had a partial or complete response to their most recent platinum-based regimen were eligible. Patients received olaparib 300mg PO bid daily, bevacizumab 15mg/kg IV q3w, and pembrolizumab 200mg IV q3w until progressive disease or unacceptable toxicity. The primary endpoint of the study was 6-month PFS rate. A simon 2-stage design was utilized. Target accrual was 22 patients in the first stage; 13 or more patients with non-progressive disease at 6 months was required to proceed to second stage. Results: 22 patients were enrolled at the first stage. Median age was 60 years old and most of the patients (90.9%) had high-grade serous carcinoma. Secondary cytoreductive surgery was performed in 6 (27.3%) patients. The objective response rate (ORR) was 68.2% and the disease control rate (DCR) was 90.9%. At the time of data analysis (data cutoff Jan 19 2022), 20 (90.9%) had non-progressive disease at 6 months. No grade 4 adverse events were reported and no treatment related adverse events leading to treatment discontinuation was observed. Additional correlative data regarding homologous recombination deficiency and PD-L1 will be presented at the meeting. Conclusions: OPEB-01 is the first trial to suggest the potential benefit of triple combination maintenance in BRCA wild-type patients. These combinations showed a manageable safety profile. Accrual is ongoing in the second stage. Clinical trial information: NCT4361370.

Efficacy, safety and cost effectiveness of reduced-dose olanzapine versus aprepitant as a part of triple-antiemetic therapy in the prevention of chemotherapy induced nausea and vomiting.

e24078 Background: In Developing world, Olanzapine at a dose of 10mg is associated with excessive somnolence. Recently, reduced dose Olanzapine 5mg has been found to be equally effective with less sedation. Hence, we intended to conduct a study comparing the efficacy, safety, and cost effectiveness of reduced dose Olanzapine 5mg vs Aprepitant. Objectives: To compare Complete response (no emesis and no rescue therapy) rates between the two groups during three periods: 0 to 24 hours (acute), 25 to 120 hours (delayed), and 0 to 120 hours (overall) after chemotherapy. To compare nausea control rates in the acute, delayed, and overall periods. To evaluate potential adverse effects and compare cost effectiveness of Olanzapine, Aprepitant. Methods: All newly diagnosed cancer patients who were scheduled to receive highly emetogenic chemotherapy (either cisplatin at a dose ≥70 mg/ m2 body surface area, with or without other chemotherapeutic agents, or doxorubicin at a dose of 60 mg/m2 plus cyclophosphamide at a dose of 600 mg /m2) and had a European Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 were randomized 1:1 to receive triple anti emetic regimen comprising of 5HT3 antagonist (Palonosetron)+Steroid (Dexamethasone) + either NK1 antagonist (either Aprepitant 125mg on day 1, 80 mg on days 2, 3 or Fosapprepitant 150mg IV on day 1) or Olanzapine 5mg once daily on days 1-4). Number of Vomiting episodes, use of rescue therapy, nausea, other adverse effects were recorded. Results: A total of 154 patients were eligible for the study, 77 in each arm. The Complete response rates for Aprepitant and Olanzapine during the acute period were 79.22% and 81.81% respectively (p &gt; 0.05), during the delayed period were 74.02% and 70.12% respectively (p &gt; 0.05), during the overall period were 74.02% and 70.12% respectively (p &gt; 0.05). Nausea control rates for Aprepitant and Olanzapine during the acute period were 74.42% and 84.82% respectively (p &gt; 0.05), during the delayed period were 45.45% and 68.83% respectively (p &lt; 0.05), during the overall period were 45.45% and 68.83% respectively (p &lt; 0.05). Most common side effect in patients receiving Olanzapine was Somnolence which was observed in 12.98% patients (CTCAE Grade 2). Most common side effect in patients receiving Aprepitant was fatigue which was seen in 6.5% patients. A 4-day course of Olanzapine costs INR-20/- while a 3-day course of Aprepitant costs INR-1000/- and a single 150mg IV Fosapprepitant costs INR 2500/-. Conclusions: In the developing world, Olanzapine 5mg can be considered as an effective, safe, and a cheaper alternate to Aprepitant as a component of triple antiemetic regimen in the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.

Raised liver enzyme in a patient receiving Helicobacter pylori triple regimen: A case report

infection remains a worldwide spread disease with a definitemorbidity and mortality.Indeed, this infection is the main cause of non-ulcer dyspepsia, peptic ulcers and gastric tumors, including bothlow-grade MALT-lymphoma and adenocarcinoma. A 65-year-old female patient visited outpatient department of Gastroenterology clinic for a routine follow-up after completion of 14-day triple drug therapy for . After a few days of empirical treatment for raised liver enzymes, her liver enzymes normalized. Clinicians should be aware about the rare adverse event during eradication treatment.

Antipseudomonal treatment decisions during CF exacerbation management

BackgroundCystic fibrosis (CF) pulmonary exacerbation (PEx) treatment guidelines suggest that Pseudomonas aeruginosa (Pa) airway infection be treated with two antipseudomonal agents. MethodsWe retrospectively studied treatment responses for STOP2 PEx treatment trial (NCT02781610) participants with a history of Pa infection. Mean lung function and symptom changes from intravenous (IV) antimicrobial treatment start to Visit 2 (7 to 10 days later) were compared between those receiving one, two, and three+ antipseudomonal classes before Visit 2 by ANCOVA. Odds of PEx retreatment with IV antimicrobials within 30 days and future IV-treated PEx hazard were modeled by logistic and Cox proportional hazards regression, respectively. Sensitivity analyses limited to the most common one-, two-, and three-class regimens, to only IV/oral antipseudomonal treatments, and with more stringent Pa infection definitions were conducted. ResultsAmong 751 participants, 50 (6.7%) were treated with one antipseudomonal class before Visit 2, while 552 (73.5%) and 149 (19.8%) were treated with two and with three+ classes, respectively. Females and participants with a negative Pa culture in the prior month were more likely to be treated with a single class. The most common single, double, and triple class regimens were beta-lactam (BL; n = 42), BL/aminoglycoside (AG; n = 459), and BL/AG/fluoroquinolone (FQ; n = 73). No lung function or symptom response, odds of retreatment, or future PEx hazard differences were observed by number of antipseudomonal classes administered in primary or sensitivity analyses. ConclusionsWe were unable to identify additional benefit when multiple antipseudomonal classes are used to treat PEx in people with CF and Pa.

Feasibility of Prolonged Calcineurin-Inhibitor Free Immunosuppression After Lung Transplantation - A Retrospective Single Center Analysis

<h3>Purpose</h3> Data on Calcineurin-inhibitor (CNI) free Immunosuppression (IS) after lung transplantation is limited to case reports. Various IS agents are reproted as alternative to CNI including proliferation signal inhibitors (PSI), belatacept and induction agents. Aim of this study was to investigate indications and outcome of CNI-free IS in a large LTx cohort. <h3>Methods</h3> A retrospective single center analysis. All patients during in follow-up after LTx with a maintenance IS without CNI were included. Reasons for conversion to CNI-free IS, complications and outcome after conversion were recorded. <h3>Results</h3> Among 2,099 patients in follow-up, 51 (2.4 %) were identified on a CNI-free IS regimen. All 51 patients (29 males, median 56 years and 6.2 years after LTx at conversion) were converted to a triple drug regimen including PSI (n=7 sirolimus, n=44 everolimus), prednisolone and an antimetabolite (n=49 mycophenolate, n=2 azathioprine). Seventeen patients had pre-existing chronic lung allograft dysfunction (CLAD) before conversion. 26 patients (52 %) had malignancy without a curative intention as a reason for conversion from conventional IS with a 1-year survival of 36%. In 11 patients with malignancy and a curative approach survival was 100% and 64% after 1 and 5 years, respectively. 7 of these were re-converted to a CNI-based regimen later. In 14 patients without malignancy, CNI-free IS was used for median 985 days. Most common non-malignant indications were polyneuropathy (n=5) and infections (n=5). 4 of these patients were re-converted to a CNI-based regimen after 97 to 338 days. In patients without malignancy and those with malignancy and curative intention (n=25), survival was 96 and 84%,1 and 5 year after conversion to CNI-free IS respectively. Four of these patients developed CLAD 146 to 1,044 days after conversion. Neuropathy improved in all affected patients. In 31 evaluable patients, median glomerular filtration rate (GFR, CKD-EPI formula) declined from 55 to 51 and 48 ml/min/1.73 m² 6 and 12 months after conversion, respectively. <h3>Conclusion</h3> Prolonged CNI-free IS based on a PSI triple regimen is feasible in selected LTx-patients. Improvement was observed in patients with neurological complications. No significant changes in GFR were noted after conversion. The role of CNI-free IS in a palliative setting of malignancy is unclear.

Clinical Characteristics and Immunosuppression Management in Kidney Transplant Recipients Infected with Severe Acute Respiratory Syndrome Coronavirus 2 Infection - An Observational Study

Background: COVID-19 infected kidney transplant patients need specialist care in tailoring their immunosuppression drugs alongside routine care. Methods and Materials: This is an observational data from a single center of 12 kidney transplant recipients (KTR) who were hospitalized with COVID-19 from April 2020 to November 2020. The demographics, COVID treatment including immunosuppressive drug regimen were reviewed. Their graft function during the stay, at the time of discharge, and 30 days after discharge was also reviewed. Results: Of 12 patients included, 83% were male patients. The median age was 37 years and the median time since transplant was 42 months. Common comorbidities were diabetes (50%), hypertension (50%), and cardiovascular disease (8%). Ninety-two percent had triple immunosuppressive regimen whereas 8% were in steroid-free protocol. Fifty percent had mild COVID, 8% had moderate disease, and 41% has severe COVID which was managed with institution-specified protocol. Steroids dose was increased in all patients. Antimetabolite was uniformly withdrawn in all patients irrespective of disease severity. Acute kidney injury was noted in 50% of patients which recovered to baseline at discharge. Graft function at 2 weeks and 30 days after discharge was stabilized close to their baseline value. Mortality was 8%. Conclusion: Reduction of immunosuppression, especially the withdrawal of antimetabolites, was found to be safe without graft rejection in KTRs.

Challenges in Heart Transplantation in COVID 19 Pandemic New Biopsy Protocol a Single Center Experience

PurposeOrthotopic heart transplantation remains the treatment of choice for endstage heart failure. In the face of the COVID19 pandemic, managing patients with advance HF before and after OHT has become an increasing challenge in both: in immunosuppression treatment and postoperative managements including biopsy protocolMethodsWe retrospectively evaluated the outcomes of all patients who underwent OTH from March 2020 to February 2021 at Silesian Heart Diseases Center, Zabrze, Poland. Due to global pandemic of COVID19 several challenges including reduced numbers of myocardial biopsies were doneResults88 patients (67 male, 21 female) underwent OHT. During this period of time the COVID-19 infections were at high level in Poland. Both donor and recipients were tested for SARSCOV2 within 48 hrs of the procedure and none tested positive. We employed strict protocol of hand hygiene, PPE usage, isolation and regular staff PCR testing. We elected to reduce the routine myocardial biopsy rate from 4to1 in first month in order to reduce exposure of the patients to the potential of COVID19 disease. All patients received a standard triple regimen of calcineurin inhibitor (tacrolimus), antimetabolite (mycophenolate mofetil) and methylprednisolone. The level of immunosuppressive medications was done every day. 20 of 88 patients underwent first biopsy at 7 - 10 days post-operatively, and 3 more biopsies at one-month interval. The first myocardial biopsies did not demonstrate acute cellular rejection. We observed acute cellular rejection (2R grade) among 3 patients (15%) in second myocardial biopsy and they were treated with methylprednisolone 1gram iv for 3 days and after we return to previous prednisone dose. Third myocardial biopsy did not demonstrated acute cellular rejection. All of patients were discharged from the hospital at day14 days, and followed up in OPD once a week till the next admission. Ultrasonography including strain echo parameters of left and right ventricle, lab tests and the level of immunosuppression were done during each OPD visit.ConclusionOHT recipients who underwent reduced numbers of myocardial biopsies appear to have reasonable outcomes (including adequate home support) compared to recipients with standard protocol. We have shown that successful heart transplantation could be performed during of COVID19 disease pandemic.

Right Ventricular Free Wall Strain RVFWS as a Predictor of Outcome in Heart Transplantation Patients with COVID19 Disease

PurposeThe aim of study was to echocardiographicly evaluate right ventricular function as a predictor of outcome in COVID 19 patients (pts) who underwent heart transplantation using RV strain and speckle tracking.Methods15 pts (mean age 47, 12 male 3 female) underwent heart transplantation from October 2020 to May 2021. All pts underwent transthoracic echocardiography for the evaluation of RV free wall longitudinal peak systolic strain RVFWSL, TAPSE, RVd1, RVd2, RVd3, FAC, TRVmax, IVC diam and S’.ResultsAll pts were PCR positive for SARSCoV2 and had cough, fever and malaise indicative of COVD19, therefore were also radiological signs of COVID19 pneumonia. Also HS troponin, procalcitonin and CRP were elevated. They were treated with antiviral drugs and immune - based therapy including corticosteroids and convalescent plasma, and received standard triple regimen of calcineurin inhibitors (tacrolimus), antimetabolite (Mycophenolan Mofetil).All echocardiographic measurements were obtained from apical 4-chamber RV with focusing on the lateral wall. RvV free wall longitudinal peak systolic strain (RVFWSL) were significantly reduced during infection compared to post infection time (-15% vs -20) and RV four-chamber strain (RV4CSL) (-11,3% vs 21%). The RV function correlated with recovery time among heart transplant patients which was longer and also correlates significantly with acute cellular rejection in myocardial biopsy (10 patients -66,6% had 2R by ISHLT) . In comparison to 2D measurement (RV diameter 28+/- 35, TAPSE 17+/-22, FAC 34+/-45) we did not observe significant difference during infection and post infection time.ConclusionThe study confirms that RV4CSL and RVFWSL are independent predictors of outcome in COVID 19 patients who undergo Heart transplantation.

Five-Year Outcome of an Early Everolimus-Based Quadruple Immunosuppression in Lung Transplant Recipients: Follow-Up of the 4EVERLUNG Study

<h3>Purpose</h3> Everolimus-based quadruple low calcineurin inhibitor (CNI) maintenance immunosuppression has been shown to be effective in preserving short-term renal function without compromising efficacy or safety after lung transplantation. However, long-term benefit remains unknown. <h3>Methods</h3> An investigator-initiated 5-year follow-up analysis of the 4EVERLUNG study (NCT01404325), comparing everolimus-based quadruple low CNI with standard triple regimen was performed. Patients who remained on the randomized drug regimen until end of the 5-year observation were analysed as per protocol (PP) population. Patients in whom the assigned regimen was switched were analysed as intention to treat (ITT) population. <h3>Results</h3> In total, 123 patients (95%) from the core study were analysed. Over the observation period in 11 patients (19%) of the standard triple regimen and in 30 patients (46%) of the quadruple low CNI regimen the assigned immunosuppressive regimen was switched (p=0.002). Estimated glomerular filtration rate at 5-year follow-up did not differ between the groups in both the ITT (56 [48, 73] vs. 58 [48, 69] mL/min; p=0.951) and PP (59 [50, 73] vs. 59 [48, 69] mL/min; p=0.946) population. Thromboembolic events occurred more frequent in the quadruple low CNI regimen (ITT: 11% vs. 24%, p=0.048; PP 11% vs. 22%, p=0.162). There was a trend for a higher CLAD-free survival for the quadruple low CNI regimen in the PP population (p=0.082). No difference in the graft-survival was found between the groups. <h3>Conclusion</h3> Initiation of an early everolimus-based quadruple low CNI regimen had no long-term benefit on renal function. The immunosuppressive efficacy and safety profile appears comparable to the standard triple regimen.