Chronic myeloid leukemia in renal transplantation patients in the era of tyrosine kinase inhibitors: A case report and review of the literature.

Lifelong immunosuppression, cytotoxic effects of some immunosuppressive drugs, and opportunistic oncogenic viruses increase malignancy risks in solid-organ recipients. The risk of myeloid neoplasms including chronic myeloid leukemia (CML) is also increased in this patient population. Tyrosine kinase inhibitors (TKIs), the key element of CML therapy should be used cautiously in transplantation patients as they may interact with calcineurin inhibitors. With this report, a 63-year-old female kidney transplant recipient who developed CML 9 years after kidney transplantation is presented. CML in this patient was treated with a slightly reduced dose of imatinib (300 mg) due to concerns of adverse events including its interaction with tacrolimus. Deep molecular response (DMR) was achieved at 12 months under imatinib treatment. The patient is still in DMR after 30 months of follow-up and she didn't experience any adverse events or acute rejection episodes. CML and the use of TKIs in kidney transplant patients are discussed with an extensive literature review. In this patient population, TKIs are generally well tolerated with achievement of treatment responses and good prognosis. Graft functions are also well maintained as long as drug interactions are monitored.

A novel homozygous SLC12A3 mutation causing Gitelman syndrome with co-existent autoimmune thyroiditis: a case report and review of the literature.

Gitelman syndrome is a rare, autosomal recessively inherited tubulopathy manifesting with hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. Common symptoms include fatigue, myalgia, reduced performance capacity, tetany, paresthesia, and delayed growth. However, as reported in the literature, diagnosis in some patients is prompted by an incidental finding of hypokalemia. GS develops due to mutations in the SLC12A3 gene, which encodes the thiazide-sensitive Na-Cl cotransporter. Many variants in the SLC12A3 gene causing GS have been reported in literature. A new pathogenic homozygous mutation (c.2612G > T), absence of hypomagnesemia, and accompanying autoimmune thyroiditis are remarkable in our patient. There are a few Gitelman syndrome cases that are complicated with autoimmune thyroiditis in the literature. In this study, we present a case of Gitelman syndrome with a novel homozygous mutation and accompanying autoimmune thyroiditis and review of the literature.

Arteriovenous fistula as the vascular access contributes to better survival of hemodialysis patients with COVID-19 infection.

BACKGROUND: While COVID-19 in chronic hemodialysis patients has high mortality and the pandemic will not end in the near future, effective follow up strategies should be implemented for these patients. Surgeries have been triaged according to their level of urgencies and arteriovenous fistula (AVF) operations were among elective surgeries. This study aimed to analyze the effect of vascular access on the outcomes of hemodialysis patients who had COVID-19. METHODS: One hundred four hemodialysis patients who had COVID-19 were retrospectively analyzed. Seventy-two of them had AVF as the vascular access while 32 of them had tunneled catheters. Inflammatory markers and outcomes of patients with AVFs and catheters were compared. A logistic regression analysis was performed in order to define factors that contribute to better outcomes in hemodialysis patients. RESULTS: COVID-19 had high mortality rate in hemodialysis patients (36.5%). Patients with catheters have higher peak ferritin levels (p = 0.02) and longer hospital stay (p = 0.00). Having AVF as the vascular access (OR = 3.36; 95% CI: 1.05-10.72; p = 0.041) and using medium cut-off dialyzers (OR = 7.99; 95% CI: 1.53-41.65; p = 0.014) were related to higher survival of the patients. COVID severity was inversely proportional to the survival (p = 0.000). CONCLUSIONS: AVFs contribute to higher survival of hemodialysis patients with COVID-19. Even in the pandemic era, end stage renal disease patients should be given the opportunity to have their vascular access properly created.

Waning of SARS-CoV-2 Vaccine-Induced Immune Response over 6 Months in Peritoneal Dialysis Patients and the Role of a Booster Dose in Maintaining Seropositivity.

INTRODUCTION: Although lower than general population, newly developed SARS-CoV-2 vaccines generate immune responses in end-stage kidney disease patients. However, the persistence of immune responses in the long term is not known yet. This study aimed to evaluate humoral immune responses in peritoneal dialysis (PD) patients over 6 months and to analyze the effects of the booster dose. METHODS: Humoral immune responses of PD patients were measured after initial SARS-CoV-2 vaccinations and after 6 months following initial vaccinations. Immune responses were compared between patients who received and did not receive booster doses. PD patients were compared with 41 hemodialysis (HD) patients and 61 healthy controls. Humoral immune responses were measured by a commercial test that detects antibodies toward the receptor-binding domain of the spike protein of SARS-CoV-2. RESULTS: Twenty PD patients were evaluated over 6 months. The initial seropositivity rate was 90.9% with inactivated vaccine and 100% with mRNA vaccine. Seropositivity decreased to 44.4% after 6 months, and a booster dose helped in maintaining the 100% of seropositivity (p = 0.005). Magnitude of humoral response at the 6th month was also higher in patients who received the third dose (1,132.8 ± 769.6 AU/mL vs. 400.0 ± 294.6 AU/mL; p = 0.015). Among patients who did not receive the third dose, those who got mRNA vaccine could maintain higher seropositivity than others who got inactivated vaccine (75% vs. 40% for PD, 81.8% vs. 50% for HD). Seropositivity and antibody levels were similar for PD and HD patients after 6 months (p = 0.24 and 0.56) but lower than healthy controls (p = 0.0013). CONCLUSION: SARS-CoV-2 vaccine-induced antibody levels and seropositivity of PD patients significantly fall after 6 months. A booster dose after around 3 months following initial immunization might help in maintaining seropositivity.

Fluctuations in Interleukin-6 Levels during Hemodialysis Sessions with Medium Cutoff Membranes: An Analysis on COVID-19 Case Series.

INTRODUCTION: Interleukin-6 (IL-6) is one of the most important mediators of inflammation. It is also the culprit for a severe disease course in COVID-19. While COVID-19 has higher mortality in hemodialysis (HD) patients, medium cutoff (MCO) membranes were previously suggested as promising tools for better patient outcomes by purging inflammatory mediators. The aim of this study was to analyze changes in IL-6 levels of HD patients who were dialyzed via MCO membranes during their COVID-19 treatments. METHODS: This is an observational study on a group of HD patients who were admitted with COVID-19 diagnosis in a university hospital and intermittently dialyzed using MCO membranes during their hospital stay. IL-6 levels of the patients were measured before and after consecutive dialysis sessions by a commercial kit. Measurements were interpreted together with the clinical data. RESULTS: Nine patients with a total of 54 measurements were evaluated. IL-6 levels were significantly higher in patients who died (median and interquartile ranges [IQRs] of IL-6 levels for patients who died and survived were 112.0 pg/mL [48.3-399.4] and 5.3 pg/mL [2.2-27.4], respectively; p < 0.001). In the comparison of changes in IL-6 levels with dialysis sessions, patients who survived had lower post-dialysis levels (median: 4.5 pg/mL; IQR: 2.2-7.6). However, IL-6 levels had a tendency to increase with dialysis sessions in patients who could not survive COVID-19 (median: 237.0 pg/mL; IQR: 53.8-418.2). CONCLUSION: This study describes over time variations in IL-6 levels of COVID-19 patients undergoing HD with MCO membranes. The trend for the changes of IL-6 levels during dialysis sessions was not uniform for all patients. Surviving patients had decreasing levels of IL-6 with consecutive dialysis sessions, while nonsurvivors had an increasing trend.

Antibody responses to inactivated SARS-CoV-2 vaccine in peritoneal dialysis patients.

INTRODUCTION: As end-stage renal disease (ESRD) patients generally have reduced responses to the vaccines, effectiveness of newly developed SARS-CoV-2 vaccines in ESRD are also matters of curiosity. We aimed to investigate the humoral responses of our peritoneal dialysis (PD) patients to the inactivated SARS-CoV-2 vaccine. METHODS: Humoral immune responses of 23 PD patients who received two doses of the inactivated SARS-CoV-2 vaccine were investigated with a commercial test that measures IgG antibodies towards receptor binding domain of SARS-CoV-2 spike protein. Seropositivity rates, antibody titers, and ESRD related clinical data were compared with 51 hemodialysis (HD) patients and 29 healthy volunteers. RESULTS: Seropositivity of PD patients with the inactivated vaccine was 95.6%. Both the rate of seropositivity and SARS-CoV-2 IgG antibody levels in PD patients were not different from the healthy controls (p = 0.85 and 0.19, respectively). While seropositivity rates were not different for PD or HD patients (p = 0.09), the magnitude of humoral responses was significantly higher in PD patients (p = 0.0001). There were no vaccine-related serious adverse events. In the 3-months clinical follow-up, none of the patients experienced SARS-CoV-2 infection. CONCLUSION: Two doses of the inactivated vaccine generate adequate humoral immune response in PD patients without any serious adverse events.

Antibody responses to the SARS-CoV-2 vaccines in hemodialysis patients: Is inactivated vaccine effective?

INTRODUCTION: Vaccines generally have reduced effectiveness in hemodialysis patients and a similar condition may also apply for the SARS-CoV-2 vaccines. The aim of this study was to analyze humoral responses of hemodialysis patients to SARS-CoV-2 vaccines. METHODS: Eighty-five maintenance hemodialysis patients who received either inactivated or mRNA SARS-CoV-2 vaccines were investigated. Antibody levels were measured by a commercial antibody kit, which detected antibodies toward receptor binding domain of the SARS-CoV-2 spike protein. Comparative analyzes were carried between vaccine groups and with a control group of 103 healthy volunteers. RESULTS: Seropositivity rate and antibody levels were significantly lower in hemodialysis patients who received inactivated vaccine (p = 0.000). While mRNA vaccine had better immunogenicity, both vaccines protected from symptomatic infection when seropositivity was achieved. DISCUSSION/CONCLUSION: When used in the same dose with the general population, inactivated SARS-CoV-2 vaccines generate reduced humoral response in hemodialysis patients. mRNA vaccines have better immunogenicity in this group.

Intraperitoneal vancomycin-induced immune thrombocytopenia.

Vancomycin is one of the drugs used in the peritonitis treatment regimen of peritoneal dialysis patients. Intraperitoneal route is generally preferred to provide rapid elimination of infective agents. Systemic toxicities of certain drugs after intraperitoneal administration are not very clear. The same also applies to vancomycin, although it has a considerable amount of systemic absorption after intraperitoneal administration. We herein report a case of severe thrombocytopenia, which was seen during the treatment of a peritonitis attack in a peritoneal dialysis patient. Culture studies revealed methicillin resistant staphylococci as the causative agent and the patient received intraperitoneal vancomycin per sensitivity analysis. Thrombocyte levels dropped abruptly to 3,900/µl after 10 days of vancomycin treatment. Clinical criteria pointed out to vancomycin-related immune thrombocytopenia. Platelet levels did not recover with initial dexamethasone treatment and platelet transfusions. In the meantime, the clinical course was also complicated with intracranial bleeding. Intravenous immunoglobulin treatment was applied and dexamethasone was switched to high-dose methylprednisolone. This latter treatment generated a response and platelet levels gradually increased to normal levels. The patient could be discharged without any sequelae. There have been two previous intraperitoneal vancomycin-related immune thrombocytopenia cases in the literature. Previous cases were reviewed, and the present case was given in comparison with the previous cases.

A comparison of antibody response in kidney transplant recipients and healthcare workers who had PCR-confirmed COVID-19 infection.

BACKGROUND: Data on antibody response following COVID-19 in kidney transplant recipients is scarce. This crosssectional study aims to investigate the antibody response to COVID-19 among kidney transplant recipients. METHODS: We recruited 46 kidney transplant recipients with RT-PCR-confirmed COVID-19 and 45 recipients without COVID-19 history. We also constructed two control groups (COVID-19 positive and negative) from a historical cohort of healthcare workers. We used age and sex-based propensity score matching to select the eligible subjects to the control groups. We measured the SARS-CoV-2 IgG levels quantitatively using the Abbott ARCHITECT system. An antibody level above 1.4 S/C was defined as positivity. RESULTS: Transplant recipients with COVID-19 had a higher BMI, and COVID-19 history in a household member was more common than that of the transplant recipient without COVID-19. IgG seropositivity rate (69.6% vs. 78.3%, p = 0.238) and the median IgG level (3.28 [IQR: 0.80-5.85] vs. 4.59 [IQR: 1.61-6.06], p = 0.499) were similar in COVID-19-positive transplant recipients and controls. Kidney transplant recipients who had a longer duration between RT-PCR and antibody testing had lower antibody levels (r = -0.532, p < 0.001). DISCUSSION: At the early post-COVID-19 period, kidney transplant recipients have a similar antibody response to controls. However, these patients' antibody levels and immunity should be closely monitored in the long term.

[Clinical Characteristics of Mild-Moderate COVID-19 Patients and Risk Factors for the Development of Pneumonia]. / Hafif-Orta Klinik Seyirli COVID-19 Hastalarinin Genel Özellikleri ve Pnömoni Gelisimi için Risk Faktörler.

Limited data exists to date on the predictors for the development of pneumonia in patients with mild and moderate coronavirus (COVID-19). In this study, it was aimed to evaluate the demographic characteristics and clinical findings of mild and moderate COVID-19 and to determine the risk factors for the development of COVID-19 pneumonia in patients admitted to the pandemic outpatient clinic of a university hospital. A total of 414 patients with laboratory confirmed COVID-19 were included. Of these, 220 (53.1%) were male, the mean age was 38.3 ± 12.7. Median duration of hospital admission from the onset of symptoms was three days (0-11). Of the confirmed COVID-19 cases, 154 (37.2%) had a history of family contact and the most common symptoms were weakness (68.4%), myalgia (61.8%), headache (56.5%), loss of smell (45.2%), loss of taste (43.2%) and anorexia (42.8%). Among females, weakness (p= 0.016), headache (p= 0.008), sore throat (p= 0.032), nausea (p= 0.003), anorexia (p= 0.045), loss of taste (p= 0.005) and loss of smell (p<0.001) were more common. Loss of taste (47.6% vs. 25%, p<0.001) and loss of smell (50% vs. 26.3%, p<0.001) were more common in patients with under the age of 50 and cough (43.4% vs. 29.3%, p= 0.003) was more common in patients with above the age of 40. Among 46 (11.1%) patients with asymptomatic COVID-19, there was no significant difference (p= 0.500) between the genders. Pneumonia was detected in 150 (43.8%) of 339 patients who underwent thorax computed tomography. In the univariate analysis; advanced age (p<0.001, odds ratio (OR)= 1.44), obesity (p<0.001 OR= 2.5), not being actively smoking (p<0.001, OR= 6.19), fever at first admission (p= 0.002, OR= 2.02), cough (p<0.001, OR= 3.26), shortness of breath (p<0.001, OR= 23.37), weakness (p= 0.042, OR= 1.63), anorexia (p= 0.009, OR= 1.79) and elevation of D-dimer (p= 0.014, OR= 1.92) were associated with the development of pneumonia. In multivariate analysis, obesity (p= 0.005, OR= 2.69), not being actively smoking (p<0.001, OR= 5.43), cough at first admission p= 0.017, OR= 2.16) and shortness of breath (p= 0.008, OR= 16.22) was determined as an independent risk factor for the development of pneumonia. CRP (p<0.001), D-dimer (p<0.001), ferritin (p<0.001) values among 108 (26.1%) patients with a body-mass index(BMI) >30 were high, and 60.9% of the patients had pneumonia (p<0.001) . CRP (p<0.001), D-dimer (p= 0.010) values were low, lymphocyte count (p= 0.001) was high among 106 (25.6%) active smokers, and 15.6% of the patients had pneumonia (p<0.001). Of the patients reported with persistent symptoms, 25.9% had loss of smell, 25% had weakness, and 23.1% had loss of taste on the seventh day; 21.1% had loss of smell, 21.1% had myalgia, and 19.7% had loss of taste on the 14th day. During their follow-up, the COVID-19 polymerase chain reaction (PCR) test was studied in 286 patients for control purposes. The median time of being negative for COVID-19 PCR test was eight days (3-56). In conclusion, symptoms may last longer than 14 days in 20- 30% of patients presenting with mild-moderate clinical findings. In addition, obesity should be considered as an important risk factor for COVID-19 pneumonia.

Seroprevalence of coronavirus disease 2019 (COVID-19) among health care workers from three pandemic hospitals of Turkey.

COVID-19 is a global threat with an increasing number of infections. Research on IgG seroprevalence among health care workers (HCWs) is needed to re-evaluate health policies. This study was performed in three pandemic hospitals in Istanbul and Kocaeli. Different clusters of HCWs were screened for SARS-CoV-2 infection. Seropositivity rate among participants was evaluated by chemiluminescent microparticle immunoassay. We recruited 813 non-infected and 119 PCR-confirmed infected HCWs. Of the previously undiagnosed HCWs, 22 (2.7%) were seropositive. Seropositivity rates were highest for cleaning staff (6%), physicians (4%), nurses (2.2%) and radiology technicians (1%). Non-pandemic clinic (6.4%) and ICU (4.3%) had the highest prevalence. HCWs in "high risk" group had similar seropositivity rate with "no risk" group (2.9 vs 3.5 p = 0.7). These findings might lead to the re-evaluation of infection control and transmission dynamics in hospitals.

Medium Cut-Off Dialysis Membranes: Can They Have Impact on Outcome of COVID-19 Hemodialysis Patients?

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 may lead to high levels of expression of inflammatory cytokines. Medium cut-off (MCO) membranes may make greater clearances for large-middle molecules (including cytokines) than low-flux (LF) membranes. In this study, we aimed to evaluate the impact of MCO membranes on outcome of COVID-19 patients on hemodialysis (HD). METHODS: Sixty COVID-19 HD patients were included in this study. The patients were categorized into 2 groups regarding type of HD membranes. Clinical data were taken from medical records. RESULTS: Initial crp and ferritin levels, which are surragates of cytokine storm and severity of disease in COVID-19, were significantly higher in MCO membrane group compared to LF group (p = 0.037 and 0.000, respectively). Although there were more patients with severe disease in MCO group, there were no significant differences regarding need for intensive care unit and death. CONCLUSION: It may be an option to use MCO membranes in HD patients with COVID-19 in order to reduce cytokine levels and prevent cytokine storm.