ABSTRACT
Introduction: Automatic drug dispensers are now widely used in critical care.1-2 They can provide information about dispensed drugs. Good practice in sedation restricts the use of sedatives and titrates doses to defined responses.3-4 Objectives: To extract drug dispenser issuing records for sedatives and link these to patient records to evaluate sedative use. Method(s): in October 2019, we introduced two Omnicell XT automated dispensing cabinets (Omnicell inc. CA, USA) into a 42 bedded general/neurological unit. ICNARC (Intensive care national audit and research centre) and CCMDS (Critical care minimum data set) data was collected using the Ward Watcher program. Dispenser issuing records for alfentanil, propofol and midazolam were obtained as Excel files for 13 months from January 2020. Output time stamps were converted to dates and times. Outputs were linked to outputs of the ICNARC and CCMDS records for the patients that the drugs were issued to. All the outputs had patients identified by their unique hospital numbers. These were used in Excel "power queries" to produce a spread sheet with a single row per patient. Multiple admissions used the first diagnosis, the final outcome and the total length of stay. The total dose of sedatives was calculated from ampoule dose and number. The duration of treatment was calculated from the first and last issues of the drug. ICNARC codes were used to identify the primary system in the admission diagnostic code and those patients admitted for COVID-19. Variables were compared using Chi Squared, Mann-Whitney U and Kruskal Wallis Tests. The significance of associations was established using Spearman's Rho. Linear regression was used to define relationships more clearly. Result(s): Table one summarises the patient characteristics with respect to all admissions during the study period and for patients who had had the studied drugs issued to them. Midazolam was used in fewer patients, they were more likely to be male, heavier (p>0001) and to die than patients receiving Propofol or Alfentanil (p>0.001). With respect to diagnostic groups, all the sedatives, particularly Midazolam (p<0.001), were more likely to be used in patients with COVID-19. The relationship between the dose of sedative drugs and patient age and weight was explored using the dose per advanced respiratory day. All three drugs had a significant but weak negative relationship with age, lower doses being given to older people (Propofol r2 = 0.02, p=0.01. Alfentanil r2 = 0.04, p=0.00. Midazolam r2 = 0.07, p=0.00.). There was also a weak but significant relationship between increasing dose of Propofol with patient weight (r2 = 0.02, p=0.01), but there was no relation between weight and doses of the other drugs. Conclusion(s): Information from automatic drug dispensers can be interpreted and combined with other datasets to produce clinically relevant information. The limited weak relationships between drug dose and age and weight suggests that sedative drugs could have been better titrated to response.
ABSTRACT
Background/Objectives: Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19 caused by SARS-CoV- 2 as they attenuate the immune response with their antiinflammatory properties. Genetic polymorphisms of glucocorticoid receptor, metabolizing enzymes or transporters may affect treatment response to dexamethasone. The aim of this study was to evaluate the association of polymorphisms in glucocorticoid pathway with disease severity and duration of dexamethasone treatment in COVID-19 patients. Method(s): Our study included 107 hospitalized COVID-19 patients treated with dexamethasone. We isolated DNA from peripheral blood and genotyped all samples for polymorphisms in NR3C1 (rs6198, rs33388), CYP3A4 (rs35599367), CYP3A5 (rs776746), GSTP1 (rs1695, rs1138272), GSTM1/GSTT1 deletions and ABCB1 (1045642, rs1128503, rs2032582 Fisher's and Mann- Whitney tests were used in statistical analysis. Result(s): The median (min-max) age of the included patients was 62 (26-85) years, 69.2 % were male and 30.8 % female and they had moderate (1.9 %), severe (83 %) or critical (15.1 %) disease. NR3C1 rs6198 polymorphism was associated with more severe disease in additive genetic model (P = 0.022). NR3C1 rs6198, ABCB1 rs1045642 and ABCB1 rs1128503 polymorphisms were associated with a shorter duration of dexamethasone treatment in additive (P = 0.048, P = 0.047 and P = 0.024, respectively) and dominant genetic models (P = 0.015, P = 0.048 and P = 0.020, respectively), while carriers of the polymorphic CYP3A4 rs35599367 allele required longer treatment with dexamethasone (P = 0.033). Other polymorphisms were not associated with disease severity or dexamethasone treatment duration. Conclusion(s): Genetic variability of glucocorticoid pathway genes was associated with the duration of dexamethasone treatment of COVID-19 patients.
ABSTRACT
Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.
ABSTRACT
Objectives: Besides in-centre ECMO care, the certificated ECMO centre of the University Hospital Regensburg (UKR) offers out-of-centre ECMO initiation with mobile equipment. During the pandemic situation, this treatment was especially meant for patients with critical cardiopulmonary failure in remote hospitals who present themselves as too unstable for interhospital transfer. We evaluated if treatment with outof-centre ECMO initiation could benefit patients;outcome, by comparing this group with a group of COVID-19 patients who received ECMO therapy at the UKR by in-hospital initiation. Method(s): Retrospective single-centre study including 169 patients who received ECMO due to COVID-19- induced cardiopulmonary failure between March 2020 till March 2022. Patients;population was separated into two groups according to the location of ECMO initiation, out-of-centre or in-centre, and into two subgroups by the used ECMO mode, venovenous (VV) or venoarterial (VA). We compared demographics, treatment duration, adverse events and patient;s outcome. The primary endpoint of the investigation was patients;survival to hospital discharge rate or death on ECMO or after ECMO explant. Result(s): Regarding the total study population, 98 (58.0%) of the 169 patients could be discharged from the UKR. Before initiation of ECMO therapy and with regard to complications during the course of intensive care, such as renal failure requiring dialysis or bleeding, there were no relevant differences between the two groups and subgroups. The out-of-centre group showed a significantly higher survival rate with 70 (63.6%) survivors out of 110 externally cannulated patients. Conclusion(s): In the study population, external ECMO cannulation was beneficial in terms of survival, although the reasons did not show significant differences between the groups. A possible approach for the good overall survival of the study groups in international comparison could be the existing centre expertise. (Figure Presented).
ABSTRACT
Acute respiratory failure (ARF) is the leading cause of death in hospitalized patients with severe forms of COVID-19. At the beginning of COVID-19 pandemic the starting respiratory protocol suggested early use of intubation and artificial lung ventilation (ALV) in patients with severe pneumonia complicated by ARF. However, after the analysis of the published studies it was noted that the pathophysiology of the development of ARF in COVID-19 had features that determine the atypical clinical pattern - "silent hypoxemia". This leads to the late onset of respiratory support (RS) and, as a result, to the lower effectiveness of non-invasive RS methods. This article discusses the creation of an algorithm for the early use of various non-invasive RS methods in patients with COVID-19 complicated by ARF, that will decrease the frequency of hospitalization to the Intensive care units, tracheal intubation and ALV, reduce the duration of treatment and improve prognosis.Copyright © 2023 IRBIS LLC. All Rights Reserved.
ABSTRACT
Objectives: The 90-day double-blind phase (DBP) of the Phase 3 EASE study demonstrated accelerated wound healing for Oleogel-S10 (birch triterpenes) versus control gel in epidermolysis bullosa (EB). Here, we report safety and total wound burden results from the 24-month open-label phase (OLP) in which all patients received treatment with Oleogel-S10. Method(s): Total wound burden was assessed using EB Disease Activity and Scarring Index (EBDASI) and Body Surface Area Percentage (BSAP). Data are reported without visit windows to reflect a realworld situation more accurately, particularly considering the COVID- 19 pandemic. Result(s): The patient population was made up of dystrophic EB (n = 178, 86.8%) and junctional EB (n = 25, 12.2%);71.7% (n = 147) of patients were aged <18 years. 141 patients (68.8%) completed the OLP. The mean (SD) treatment duration for all patients was 584.7 (246.1) days. Adverse events were reported in 77.1% of all patients in the OLP versus 81.7% of those receiving Oleogel-S10 in the DBP. Mean BSAP for patients treated with Oleogel-S10 in the DBP reduced from 12.1% at study entry to 6.1% with 27 months of treatment. Similarly, the mean EBDASI skin activity score in the Oleogel-S10 group improved from 19.6 to 15.1 after 27 months. In addition, reductions in both BSAP and EBDASI from OLP baseline were observed in patients who transitioned from control gel to Oleogel-S10 in the OLP. Discussion(s): These data support a reassuring long-term safety profile of Oleogel-S10. Furthermore, the reduction in wound burden previously reported with 15 months of Oleogel-S10 treatment is maintained to the end of OLP. This is encouraging given the nature of this chronic genetic disorder in which there is regular cycling of patients' fragile wounds.
ABSTRACT
The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.
ABSTRACT
Considering the commonality of the pathogenetic links of the critical forms of COVID-19 and influenza AH1N1pdm09 (cytokine over-release syndrome), the question arises: will the predictors of an unfavorable outcome in patients on mechanical ventilation and, accordingly, the universal tactics of respiratory support in these diseases be identical? Objective. In a comparative aspect, to characterize patients with influenza AH1N1pdm09 and COVID-19 who were on mechanical ventilation, to identify additional clinical and laboratory risk factors for death, to determine the degree of influence of respiratory support (RP) tactics on an unfavorable outcome in the studied category of patients. Patients and methods. Patients treated on the basis of resuscitation and intensive care departments of the State Budgetary Healthcare Institution "SKIB" in Krasnodar and the State Budgetary Healthcare Institution "IB No 2" in Sochi were studied: group 1 - 31 people with influenza AH1N1pdm09 (21 people died - subgroup 1A;10 people survived - subgroup 1B) and group 2 - 50 people with COVID-19 (29 patients died - subgroup 2A;21 people survived - subgroup 2B). All patients developed hypoxemic ARF. All patients received step-by-step tactics of respiratory support, starting with oxygen therapy and ending with the use of "traditional" mechanical ventilation. Continuous variables were compared in subgroups of deceased and surviving patients for both nosologies at the stages: hospital admission;registration of hypoxemia and the use of various methods of respiratory therapy;development of multiple organ dysfunctions. With regard to the criteria for which a statistically significant difference was found (p < 0.05), we calculated a simple correlation, the relative risk of an event (RR [CI 25-75%]), the cut-off point, which corresponded to the best combination of sensitivity and specificity. Results. Risk factors for death of patients with influenza AH1N1pdm09 on mechanical ventilation: admission to the hospital later than the 8th day of illness;the fact of transfer from another hospital;leukocytosis >=10.0 x 109/l, granulocytosis >=5.5 x 109/l and LDH level >=700.0 U/l at admission;transfer of patients to mechanical ventilation on the 9th day of illness and later;SOFA score >=8;the need for pressor amines and replacement of kidney function. Predictors of poor outcome in ventilated COVID-19 patients: platelet count <=210 x 109/L on admission;the duration of oxygen therapy for more than 4.5 days;the use of HPNO and NIV as the 2nd step of RP for more than 2 days;transfer of patients to mechanical ventilation on the 14th day of illness and later;oxygenation index <=80;the need for pressors;SOFA score >=8. Conclusion. When comparing the identified predictors of death for patients with influenza and COVID-19 who needed mechanical ventilation, there are both some commonality and differences due to the peculiarities of the course of the disease. A step-by-step approach to the application of respiratory support methods is effective both in the case of patients with influenza AH1N1pdm09 and patients with COVID-19, provided that the respiratory support method used is consistent with the current state of the patient and his respiratory system, timely identification of markers of ineffectiveness of the respiratory support stage being carried out and determining the optimal moment escalation of respiratory therapy.Copyright © 2022, Dynasty Publishing House. All rights reserved.
ABSTRACT
Background: The interaction between checkpoint inhibitors (CPI) and Sars-COV-2 vaccines has been understudied. One potential complication in pts receiving CPI is immune-mediated adverse events (irAEs) resulting from overactivation of the immune system. It is unknown whether concurrent CPI and Sars-COV-2 vaccine administration increases the risk of irAEs. This retrospective study examined the incidence of severe irAEs in cancer patients receiving CPI therapy at the time of vaccination against Sars CoV-2. Method(s): Following IRB approval, pts with solid tumors who received any approved CPI since FDA authorization of the COVID-19 vaccine in December 2020 were identified via institutional electronic health record. Pts who received one or more doses of an authorized vaccine within 60 days of CPI treatment were included. The primary endpoint was to evaluate the incidence of severe irAE (one or more of the following: grade 3 AE or above, multi-system involvement, need for hospitalization). Secondary endpoints included time between CPI and vaccination, need for immunosuppressive therapy, and rate of discontinuation of CPI due to irAE. Data was analyzed using descriptive statistics. Result(s): 290 pts with bladder, head/neck, liver, skin (melanoma, SCC), renal, and gynecologic cancer were included in analysis. The median age was 67 years (IQR: 59.0-74.0) and 66% pts were male. At the time of vaccination, 201 pts (69.3%) received CPI monotherapy, 53 pts (18.3%) received combination (combo) CPI therapy, and 36 pts (12.4%) received other therapies (chemo, TKIs, etc.) with CPI. The vaccine manufacturer was Pfizer Bio-N-Tech in 162 pts (55.9%), Moderna in 122 pts (42.1%), and Johnson and Johnson in 6 pts (2.1%). The number of vaccinations received was >/= 3 in 214 pts, 2 in 64 pts, and 1 in 11 pts. 30 pts (11.5%) experienced severe irAEs following vaccination. The rate of severe irAEs was 10.3% (30/290) in the total population [6% (12/201) with CPI monotherapy, 19% (10/53) with combo CPI, and 22% (8/36) in the combo CPI-other group]. Severe irAEs occurred after the first vaccine dose in 5 pts (16.7%), second dose in 16 pts (53.3%), and third dose in 9 pts (30%) pts. The median time between CPI treatment and vaccination in pts who experienced irAE was15.5 days (IQR: 10.2-23.0). Hospitalization was required for 19 patients (63.3%). 24 pts (80.0%) required immunosuppressive therapy with a median therapy duration of 98.5 days (IQR 40.2-173.0). 16 pts (53.5%) discontinued CPI therapy following severe irAEs Conclusion(s): In this retrospective study, we observed a 10.3% rate of severe irAE in cancer pts receiving CPI concurrently with COVID-19 vaccines. Further investigation in pts with additional cancer types is warranted to help determine best practice guidelines for COVID-19 vaccination in cancer patients receiving CPI.
ABSTRACT
Background: B-cell lymphoma-2 (Bcl-2) proteins play an important role in multiple myeloma (MM) cell survival and represent an attractive therapeutic target. In prior trials, a subgroup analysis of patients with t(11;14)-positive relapsed/refractory (R/R) MM showed the combination of a Bcl-2 inhibitor, a proteasome inhibitor, and dexamethasone improved progression-free survival with no increased mortality. BGB-11417, a Bcl-2 inhibitor, is more potent and selective than venetoclax. BGB-11417- 105 (NCT04973605) is a phase 1b/2 study assessing the safety and efficacy of BGB-11417 monotherapy, in combination with dexamethasone, or with dexamethasone+carfilzomib in patients with t(11;14)-positive R/R MM. Preliminary safety results for the combination of BGB-11417 + dexamethasone are presented. Method(s): Eligible patients had t(11;14)-positive R/R MM and had been exposed to a proteasome inhibitor, immunomodulatory agent, and anti-CD38 therapy. Patients received 80-, 160-, 320-, or 640-mg BGB-11417 daily with 40-mg dexamethasone weekly until death, intolerability, or disease progression. Dose escalation was guided by a mTPI-2 design and overall review by a safety monitoring committee. Pharmacokinetics (PK) were also assessed. Result(s): As of 1 July 2022, 10 patients were enrolled in the 80-, 160-, and 320-mg (3 patients each) and 640-mg (1 patient) dose-escalation cohorts of BGB-11417 + dexamethasone. The median age was 69 years (range, 52-81) and median prior lines of therapy was 3 (range, 1-5). The median treatment duration was 3.2 months (range, 0.5-6.5). No patients experienced dose-limiting toxicity at any dose level. Three patients died whilst on study: 1 due to COVID-19 complications 157 days after treatment discontinuation (day 208), 1 due to progressive disease 50 days after treatment discontinuation (day 89), and 1 due to COVID-19 whilst on study treatment (day 78). No deaths were associated with study treatment. Two patients experienced Grade >= 3 treatment-emergent adverse events (TEAEs). One patient in the 160-mg cohort experienced Grade 3 increase in liver enzymes and lymphopenia. One patient in the 320-mg cohort experienced Grade 3 lymphopenia. The most common TEAEs were insomnia (50%), fatigue (30%), arthralgia (20%), back pain (20%), lymphopenia (20%), and nausea (20%). BGB-11417 exposure increased dose-dependently from 80 mg to 320 mg with high interpatient PK variability. BGB-11417 exposures after single and multiple doses appeared similar, indicating limited accumulation. Conclusion(s): BGB-11417 plus dexamethasone was generally well-tolerated in patients with R/R MM harbouring t(11;14) at doses <=640 mg. Efficacy data are forthcoming. Recruitment is ongoing in the US, Australia, and New Zealand;the BGB-11417, dexamethasone, and carfilzomib combination arm will open in the future.
ABSTRACT
Background/Aims The use of Janus Kinase Inhibitors (JAKi) has been gradually increasing overtime in the management of rheumatoid arthritis (RA) and other inflammatory arthritis and these appeal to patients. being oral agents. Nevertheless, rheumatologists have become cautious about their use since recent trials have shown safety concerns about VTEs, MACE and malignancies. Methods We decided to study use of JAKi at our centre in Princess of Wales Hospital Bridgend. The aim was to assess whether appropriate patients were selected (considering cautions about MACE, VTEs and malignancies). We also wanted to see whether all patients had required pretreatment safety testing and post-treatment monitoring performed. Results These were 70 patients;59 were females and 11 were males. All of them were diagnosed as RA. Average age was 61.1 years (20-85), average duration of disease 129.9 months (16-340) and average duration of treatment was 58.1 weeks. The most common JAKi being used was baricitinib (84%) followed by tofacitinib (12%) and upadacitinib (4%). 50% patient were on concomitant csDMARDs among whom two-thirds were on methotrexate. Looking at previous biologic use, 9 patients were biologic naive, 22 had one biologic, 15 had two biologics used in the past. All patients were appropriately selected (severe RA and no significant risk factors for MACE, VTEs and malignancies). All patients had pre-treatment Hepatitis B, Hepatitis C, latent TB, FBC and LFTs checked. All patients had FBC and LFTs monitored post treatment. No patient developed VTE, MACE or cancer on treatment. 84.2% patients had lipids tested before starting JAKi. 22.8% patients had abnormal lipids before Rx initiation and 62.5% of these were on lipid lowering Rx. All patients had lipids tested post treatment, but the timing was quite variable and only 62.5% of patients had lipids tested on the recommended time. There were 2 deaths recorded in this cohort. One of those was an 80-year-old RA patient on baricitinib 2mg OD, who died due to chest infection on the background of ILD. He was not on steroids or csDMARDs. The second patient was 63 years' old (on baricitinib 4mg OD), and died due to respiratory sepsis, and was also on azathioprine. She had RA with advanced ILD. The reasons for discontinuing JAKi were inefficacy (46%), side effects (39%) and both inefficacy and side effects (15%). 41.4%of patient experienced side effects due to JAKi. These included infection 28%, deranged lipids 17%, cytopenia 14%, deranged LFTs 14%, GI side effects 10%, skin rash 7% and varicella zoster 3%. Conclusion There has been steady increase in the use of tsDMARDs for RA and other rheumatic conditions. Due to short half-life, these drugs became a popular choice during COVID-19 pandemic but on the other hand safety monitoring became extremely challenging during this time.
ABSTRACT
Intro: The ongoing pandemic caused by the SARS-CoV-2 virus has brought many new insights into medicine. During the first months of the pandemic, when there were no comprehensive guidelines for precise antimicrobial therapy, empirical overuse of broad-spectrum antibiotics was observed. Which resulted in the development of clostidium infection in certain cases. In our report, we address 83 cases of clostridial colitis in post-covid patients from 3/2020 to 3/2021 and their specific therapy. Method(s): Retrospective analysis of risk factors for clostridial infection and therapy of clostridial colitis. Finding(s): In the period 3/2020-3/2021, 9617 patients were diagnosed with SARS-CoV-2 virus infection in our hospital, of which 1247 were hospitalized. In 83 cases, clostridial colitis occurred during or after the covid infection had resolved. Mortality in this group was 17%, which corresponds to 14 patients. Previous empirical administered antiobiotics in COVID-19 infection contributed to the development of clostridial colitis in case of 22 patients (27%) by clarithromycin, in 14 pacients (17%) by penicillins and by 3rd generation cephalosporins in 9 patients (11%). The average duration of therapy with broad-spectrum antibiotics was 15.63 days (+-8.99). Other risk factors we observed are: PPI use (25%), active malignant disease (10%), previous glucocorticoid therapy (22%). Vancomycin was used in clostridial infection therapy in 47% (39), metronidazole in 31% (25) and fidaxonicin in 7% (6). In the group, we observed recurrence of clostridium difficile infection in 14% of patients and FMT was performed in 6 patients. Conclusion(s): This study shows a higher percentage of clostridial infection in cases of long-term therapy with broad-spectrum antibiotics. It also points to the effect of specific antimicrobial therapy for infection caused by the bacterium Clostridium difficile and the possibility of using fecal bacteriotherapy.Copyright © 2023
ABSTRACT
Introduction: Gastrointestinal tract involvement from herpes simplex virus is commonly associated with esophagitis. However, herpes simplex infection of the stomach is very rare with only a handful of cases being reported in immunocompromised patients. We present a case of herpes gastritis causing gastric outlet obstruction in an otherwise healthy, immunocompetent individual. Case Description/Methods: A 37-year-old male with a recent past medical history of COVID-19 infection, presented to the hospital with intractable nausea, vomiting, bloating, and early satiety for two days. Upon evaluation, CBC and CMP were remarkable for a WBC of 12.5 k/mm3 and ALT and AST of 124 U/L and 129 U/L, respectively. Lipase was 373 U/L. A CT abdomen/pelvis w/contrast showed circumferential wall thickening with edematous changes in the antrum consistent with localized inflammatory response. There was suspicion for gastric lymphoma and patient was admitted for further workup. An EGD was performed which showed exudative esophagitis and antral wall edema with luminal narrowing of gastric antrum. Endoscopic ultrasound (EUS) showed a 2.5 x 3 cm antral wall lesion worrisome for linitis plastica. Esophageal biopsies showed focal cytologic changes consistent with herpes esophagitis. The FNA of the gastric antral wall showed multinucleation of the basal cell layer with classic ground glass nuclei, consistent with herpes infection. No dysplasia or malignancy was seen. Both HSV1 and HSV2 IgG were elevated. HSV IgM was normal. A HSV PCR was ordered but never resulted. Patient was started on Valacyclovir 1 g PO BID for 10 days. He underwent a follow-up EGD 3 months later which showed complete resolution of the gastric antral changes (Figure). Discussion(s): Herpes gastritis is extremely rare. Literature review has revealed only 3 case reports of herpes gastritis;and all involved immunocompromised patients. To the best of our knowledge, this is the first case of herpes gastritis in an immunocompetent patient. Our patient presented with symptoms of gastric outlet obstruction which was caused by local inflammation from herpes simplex. It is unclear if having a COVID 19 infection altered patient's immunity and lead to herpes gastritis. This may need further investigation. No established guideline exists for treatment duration. Our patient received 10-day course of Valacyclovir, and his symptoms improved. Furthermore, patient had complete resolution of the herpes infection on follow-up EGD, indicating adequate treatment response.
ABSTRACT
Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).
ABSTRACT
Post-infectious immunosuppression may cause repeated hospitalization after COVID-19 pneumonia. The results of the observational study of the Raphamin use for immunotherapy in the recovery period of COVID-19 pneumonia are presented. Aim(s): to estimate efficiency of Rafamin usage in patients who have completed the course of inpatient treatment for coronavirus pneumonia. Material and methods. Thirty patients aged 18 to 80 years after hospital treatment of COVID-19 pneumonia were included and randomized into 2 groups (1: 1). All patients received anticoagulants, antioxidants, metabolic drugs. Patients of the 1st group (n=15) were additionally prescribed Raphamin for 5 days. The primary endpoint was the number of repeated hospitalizations due to consequences of COVID-19 and/or new cases of acute respiratory infection for 28 days of follow-up. In addition, dynamic of immune and inflammatory markers (absolute lymphocyte count, C-reactive protein), proportion of patients with immune dysregulation, and duration of symptoms associated with COVID-19 were assessed. Results. The number of hospitalized patients in group 1 was 0 (vs 5 in group 2, p=0.0421). Study therapy reduced the risk of repeated hospitalizations in 1.44 times [relative risk 1.44;95% confidence interval 0.91-2.28];duration of breathlessness decreased from 24.5 to 15.3 days (p=0.0108), and duration of fatigue reduced from 23.6 to 16.8 days (p=0.0452). The proportion of patients with immune markers normalization was 2 times higher than in the comparison group on 14 day of observation. Conclusion. The immunomodulatory therapy may be recommended during the recovery period of COVID-19 pneumonia.Copyright © Eco-Vector, 2022.
ABSTRACT
On December 13, 2020, Yutian County People's hospital reported one imported malaria case in Hotan, Xinjiang. The patient had worked and lived in Yaounde, Cameroon, from January to September 2020. He was infected with malaria twice in March and May 2020. Antimalarial treatment was administrated by the team doctor for 2-3 days in each treatment. The treatment was stopped after the symptoms improved. The patient returned to China on September 16 and was hospitalized on December 13 due to a high fever of 39! and upper respiratory symptoms. Multiple detections of COVID-19 nucleic acid showed negative results. Peripheral blood from the patient was taken for Plasmodium rapid diagnostic test (RDT), which showed a positive result suggesting non Plasmodium falciparum infection. Ring stage P. ovale was found in the blood smear. Nested PCR showed positive for P. ovale. A diagnosis of imported ovale malaria was made. The patient was administrated with 4 dihydroartemisinin piperaquine tablets and 3 primaquine phosphate tablets daily. The malaria parasite test became negative after 8 days of treatment. The patient was followed up for 3 months after discharge and had no symptoms of chills or fever.Copyright © 2022, National Institute of Parasitic Diseases. All rights reserved.
ABSTRACT
Introduction: Advanced MZL is generally incurable, with periods of remission and relapse. Zanubrutinib (BGB-3111), a potent and highly specific next-generation Bruton tyrosine kinase (BTK) inhibitor, was approved in the US and Canada for R/R MZL based on the MAGNOLIA primary analysis (BGB- 3111-214;NCT03846427);here, the final MAGNOLIA analysis is presented. Method(s): This was a phase 2, multicenter, single-arm study of adult patients (pts) with R/R MZL (>=1 prior CD20-directed therapy). Zanubrutinib (160 mg twice daily) was given until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) by independent review committee (IRC) per Lugano classification. Secondary endpoints were investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy was assessed by positron emission tomography (PET)-based Lugano criteria for IRC-confirmed fluorodeoxyglucose (FDG)-avid disease at baseline;non-avid disease was assessed by computed tomography (CT)-based criteria. Result(s): As of May 4, 2022, 68 pts were treated (median age=70 y [range 37-95];>=75 y=27.9%). MZL subtypes included extranodal (38.2%), nodal (38.2%), splenic (17.6%), and unknown (5.9%). The median number of prior therapies was 2 (range 1-6);32.4% of pts had disease refractory to last therapy, most (89.7%) had prior chemoimmunotherapy, and 7 (10.3%) had rituximab monotherapy as their only prior treatment. Sixty-one pts (89.7%) had FDG-avid disease. After a median follow-up of 28.0 mos (range 1.6-32.9) and a median treatment duration of 24.2 mos (range 0.9-32.9), 66 pts were efficacy- evaluable. IRC-assessed ORR (complete response [CR]+partial response [PR]) was 68.2% (CR=25.8%). By subtype, (Figure Presented)(Figure Presented)ORR/CR rates were 64.0%/40.0% (extranodal), 76.0%/20.0% (nodal), 66.7%/8.3% (splenic), and 50.0%/25.0% (unknown). Median DOR, PFS, and OS were not reached. Over 70.0% of pts were alive or progression-free after 2 years (Figure). Sensitivity analysis using only CT-based criteria (n=66) showed an ORR of 66.7% and CR of 24.2%. The most common treatment-emergent AEs were bruising (23.5%), diarrhea (22.1%), and constipation (17.6%). Neutropenia (8.8%) and COVID-19 pneumonia (5.9%) were the most common Grade >=3 AEs. Five pts (7.4%) died due to unrelated AEs: COVID-19 pneumonia=2, acute myeloid leukemia=1, myocardial infarction=1, septic encephalopathy=1. Hypertension occurred in 3 pts (4.4%), atrial fibrillation and atrial flutter in 1 pt (1.5%) each;none led to treatment withdrawal. One pt (1.5%) had a Grade 3 gastrointestinal hemorrhage while receiving rivaroxaban. None of the pts required dose reduction. Conclusion(s): In this final analysis with over 2 years of median follow-up, zanubrutinib continues to demonstrate durable disease control and was generally well tolerated, with no new safety signals observedCopyright © 2023 American Society for Transplantation and Cellular Therapy
ABSTRACT
Hepatitis A is a common viral infection worldwide that is transmitted via the fecal-oral route. Since the introduction of an efficient vaccine, the incidence of infection has decreased but the number of cases has risen due to widespread community outbreaks among unimmunized individuals. Classic symptoms include fever, malaise, dark urine, and jaundice, and are more common in older children and adults. People are often most infectious 14 days prior to and 7 days following the onset of jaundice. We will discuss the case of a young male patient, diagnosed with acute hepatitis A, leading to fulminant hepatitis refractory to conventional therapy and the development of subsequent kidney injury. The medical treatment through the course of hospitalization was challenging and included the use of L-ornithine-L-aspartate and prolonged intermittent hemodialysis, leading to a remarkable outcome. Hepatitis A is usually self-limited and vaccine-preventable;supportive care is often sufficient for treatment, and chronic infection or chronic liver disease rarely develops. However, fulminant hepatitis, although rare, can be very challenging to manage as in the case of our patient.Copyright © 2023 The Author(s).
ABSTRACT
Reports an error in "The impact of patient's fear of COVID-19 infection on neurology service in University Hospital Center Sestre Milosrdnice during COVID-19 epidemic outbreak" by Arijana Lovrencic-Huzjan and Marina Roje-Bedekovic (Archives of Psychiatry Research: An International Journal of Psychiatry and Related Sciences, 2021, Vol 57[2], 167-176). In the original article, one of the authors name was missing. The correction is given in the erratum. (The following of the original article appeared in record 2022-62540-005). Increasing evidence suggests that patients with medical emergencies are avoiding the emergency department because of fear of coronavirus disease 2019 (COVID-19) infection, leading to increased morbidity and mortality due to other diseases. In order to analyse the impact of patient's fear of COVID-19 on the admittance rate of stroke patients and severity of neurological diseases, we compared the stroke admittance rate, numbers of thrombectomies and thrombolysis and hospitalization refusal rate during the time period from March 1st until June 30th 2020 in temporal relationship with the rising numbers of COVID-19 cases in Croatia. We assessed the patients' neurologic disease severity measured by ventilation time and mortality rate in the same time period. We compared the data with the data obtained from the same time period in 2019. We observed dramatically decreased presentation in Neurologic Emergency Department due to stroke and neurologic disease in 2020 compared to 2019, increased refused hospitalization rate and similar stroke treatment rate despite bigger catchment area. Greater neurologic disease severity with almost 40% increased ventilation time and double mortality rate during the same time was observed. During the outbreak of COVID-19 epidemic, fear of infection had significant impact on neurologic service leading to decreased presentation to NED, resulting in increased stroke or neurologic disease-related morbidity and mortality. (PsycInfo Database Record (c) 2023 APA, all rights reserved)