Preoperative COVID-19 Vaccination is Associated with Decreased Perioperative Mortality after Major Vascular Surgery (preprint)

Background: The objective of this study was to examine the effect of COVID-19 vaccination on perioperative outcomes after major vascular surgery. Methods: This is a multicenter retrospective study of patients who underwent major vascular surgery between December 2021 through August 2023. The primary outcome was all-cause mortality within 30 days of index operation or prior to hospital discharge. Multivariable models were used to examine the association between vaccination status and the primary outcome. Results: Of the total 85,424 patients included, 19161 (22.4%) were unvaccinated. Unvaccinated patients were younger compared to vaccinated patients (mean age 68.44 +/- 10.37 years vs 72.11 +/- 9.20 years, p <.001) and less likely to have comorbid conditions, including hypertension (87.2% vs 89.7%, p <.001), congestive heart failure (14.5% vs 15.9%, p <.001), chronic obstructive pulmonary disease (35.7% vs 36.3, p <.001) and renal failure requiring hemodialysis (1.4% vs 1.7%, p = .005). After risk factor adjustment, vaccination was associated with decreased mortality (OR 0.7, 95% CI 0.62 - 0.81, p <.0001). Stratification by procedure type demonstrated that vaccinated patients had decreased odds of mortality after open AAA (OR 0.6, 95% CI 0.42-0.97, p = 0.03), EVAR (OR 0.6, 95% CI 0.43-0.83, p 0.002), CAS (OR 0.7, 95% CI 0.51-0.88, p = 0.004) and infra-inguinal lower extremity interventions (OR 0.7, 95% CI 0.48-0.96, p = 0.03). Conclusions: COVID-19 vaccination is associated with reduced perioperative mortality in patients undergoing vascular surgery. This association is most pronounced for patients undergoing aortic aneurysm repair, carotid stenting and infrainguinal bypass.

Cold case: COVID-19-triggered type 1 cryoglobulinemia (preprint)

A 42-year-old male was referred to the internal medicine department because of renal failure and persistent malaise after a recent SARS-CoV-2 infection. Blood results showed anemia and severe renal insufficiency (hemoglobin of 6.4 mmol/l and a creatinine of 194 umol/l). Additional tests revealed a type I cryoglobulinemia with a cryoprecipitate composed of biclonal IgM (kappa and lambda). Further investigations on the cryoprecipitate revealed that the immunoglobulins were directed against SARS-CoV-2 antigens. In the meanwhile, our patient noticed improvement of his symptoms accompanied by resolution of laboratory abnormalities. Three months later, the cryoglobulin could no longer be detected. Type 1 cryoglobulinemia is usually associated with lymphoproliferative disorders and is characterized by various symptoms caused by cryoprecipitates occluding small blood vessels. This is, to our knowledge, the first case of type I cryoglobulinemia with proven precipitation of SARS-CoV-19 antibodies. COVID-19 induced cryoglobulinemia appears to have a mild disease course and to be self-limiting upon viral clearance.

A Phase 2, randomized, double-blind, placebo-controlled multi-center trial sub-study for the clinical effects of paridiprubart treatment in hospitalized critically ill patients with COVID-19 ARDS (preprint)

Background: Coronavirus disease 2019 (COVID-19) mortality is predominantly due to acute respiratory distress syndrome (ARDS). There are currently limited treatment options for ARDS, a life-threatening condition with different etiologies, secondary to inflammation-induced lung injury. Paridiprubart is a monoclonal antibody that inhibits Toll-like Receptor 4 (TLR4), a key player in ARDS pathophysiology. Methods: This was a prespecified sub-study of a randomized, double-blind, placebo-controlled, Phase 2 trial evaluating the efficacy and safety of paridiprubart in COVID-19 patients with ARDS receiving invasive mechanical ventilation and additional organ support. Efficacy outcomes were 28- and 60-day all-cause mortality, and improvement in COVID-19 severity and ventilation-free days at 28-days post-treatment. Results: Thirteen (13) and twenty (20) patients received paridiprubart and placebo, respectively. The groups were comparable for demographics and baseline parameters, except for higher kidney failure incidence and use of immune modulators and antivirals, and lower corticosteroids use in the paridiprubart group. Mortality at 28-days post-treatment was 7.7% (1/13) in the paridiprubart group versus 40.0% (8/20) for placebo (OR=0.125; 95% CI, 0.013-1.160; P=0.067; P[bootstrap]=0.011). 60-day mortality was 23.1% (3/13) in paridiprubart-treated patients and 45.0% (9/20) in placebo patients (OR=0.367; 95% CI, 0.077-1.749; P=0.208; P[bootstrap]=0.162). Mean survival time was 55.78 days for paridiprubart recipients compared to 41.44 days for placebo patients (HR=0.386; 95% CI, 0.077-1.436; P=0.156; P[bootstrap]=0.083). Although not statistically significant, results for other efficacy measures favored paridiprubart. Incidence of adverse events was similar in both groups. Conclusions: In COVID-19 patients with ARDS requiring invasive ventilation and organ support, paridiprubart was efficacious in preventing mortality and improving clinical outcomes, with no safety concerns.

Exploring Australian pharmacists' views toward reducing the risk of medicines-related harm in aged care residents.

Medicines-related harm is common in older people living in residential aged care facilities (RACFs). Pharmacists offering services in the aged care sector may play a key role in reducing medicines-related injury. This study aimed to explore Australian pharmacists' views toward reducing the risk of medicines-related harm in older residents. Qualitative, semi-structured interviews were conducted with 15 Pharmacists across Australia providing services (e.g., through the provision of medication reviews, supplying medications, or being an embedded pharmacist) to RACFs identified via convenience sampling. Data were analyzed by thematic analysis using an inductive approach. Medicines-related harm was thought to occur due to polypharmacy, inappropriate medicines, anticholinergic activity, sedative load, and lack of reconciliation of medicines. Pharmacists reported that strong relationships, education of all stakeholders, and funding for pharmacists were facilitators in reducing medicines-related harm. Pharmacists stated that renal impairment, frailty, staff non-engagement, staff burnout, family pressure, and underfunding were barriers to reducing medicines-related harm. Additionally, the participants suggested pharmacist education, experience, and mentoring improve aged care interactions. Pharmacists believed that the irrational use of medicines increases harm in aged care residents, and medicines-specific (e.g., sedative load) and patient-specific risk factors (e.g., renal impairment) are associated with injuries in residents. To reduce medicines-related harm, the participants highlighted the need for increased funding for pharmacists, improving all stakeholders' awareness about medicines-associated harms through education, and ensuring collaboration between healthcare professionals caring for older residents.

Patients' experience of undergoing maintenance hemodialysis. An interview study from Ethiopia.

BACKGROUND: People with kidney failure require renal replacement therapy in the form of dialysis or a kidney transplant for survival. Many facets of their life, both within and outside the dialysis unit, are impacted by the management of this disease. It is important to comprehend the experiences of people undergoing hemodialysis in order to improve the care provided to them. Therefore, this study aimed to explore the experiences of patients undergoing maintenance hemodialysis in Ethiopia. METHODS: A qualitative descriptive study was conducted at two healthcare facilities in Ethiopia. Individual interviews with 15 participants (men and women aged 19-63), undergoing hemodialysis in Ethiopia, were analyzed using reflexive thematic analysis. RESULTS: The analysis resulted in five themes: Feeling grateful, Facing a restricted life, a Supportive environment, Dreaming of a transplant, and Leading a hassled life. The subthemes include Trust in treatment, Faith in God, Challenging fluid and dietary restrictions, Being too fatigued to socialize, Being stigmatized, Family and social support, Supportive healthcare, Lacking a donor and sponsor, COVID-19 as a barrier, Financial constraints, Inaccessibility to care and transport and Access line implantation. Despite being dependent on a machine and having to deal with food and fluid restrictions as well as financial challenges, participants were hopeful and dreamed of a transplant. CONCLUSION: From the study's participants, it was discovered that the experiences of people with kidney failure undergoing hemodialysis were generally, considerably negative narratives. Based on the results we recommend development of multidisciplinary teams to better meet patients' physical, emotional, and social needs while undergoing hemodialysis. Such a team should also involve the patient's family members when caring for patients on hemodialysis.

Simultaneous Quantification of Nirmatrelvir/Ritonavir in Human Serum by Lc-Ms/Ms (preprint)

In December 2021, the U.S. Food and Drug Administration (FDA) granted emergency authorization for Paxlovid® as an antiviral treatment for COVID-19. Paxlovid® is composed of two tablets, nirmatrelvir and ritonavir. Dose adjustment is necessary in cases of renal insufficiency. The aim of present study is to establish a LC-MS/MS method for simultaneous determination of nirmatrelvir/ritonavir in human serum for therapeutic drug monitoring. Internal standard saquinavir was added in 25 μl human serum samples, and then the samples were precipitated with methanol. The analytes were separated by gradient elution on a C18 column, using a mobile phase of 0.1% formic acid-water and methanol, at a flow rate of 0.4 ml/min. The injection volume was 2 μl, and the analysis time was 5 min. The determination of the analytes was performed by electrospray ionization in positive mode by full mass monitoring. The detected ions of nirmatrelvir, ritonavir and saquinavir were m/z 500.24792, 721.32004 and 671.39155, respectively. The linear concentration range for nirmatrelvir was 78.13~20000 ng/ml, for ritonavir was 15.63~4000 ng/ml (r2>0.9900). The accuracy ranged from 87.45%~104.63%, and the intra-day and inter-day precision RSD was < 15%. The recovery of Nirmatrelvir ranged from 98.72%~109.83%, and that of ritonavir was 95.41%~112.36%. The matrix effect of Nirmatrelvir was 88.31%~97.73%, and that of ritonavir was 85.17%~103.05%. This method was used to measure the trough concentrations of nirmatrelvir/ritonavir in 17 patients. The trough concentration of nirmatrelvir was 1331.7~8352.5 ng/ml, and that of ritonavir was 53.4~1325.5 ng/ml, with large individual differences. The method is simple, sensitive, specific, and reproducible, and can be used for monitoring the blood concentration and pharmacokinetic study of nirmatrelvir/ritonavir in COVID-19 patients.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

Review of the present features and the infection control challenges of COVID-19 pandemic in dialysis facilities.

The COVID-19 has swept the world causing suffering, death, loss, and massive economy damage. The dialysis population is vulnerable and the dialysis facility is critical in maintaining operations and avoiding disease transmission. The present information regarding the clinical features of COVID-19 infection in the dialysis population was collected, and the useful measures of COVID-19 infection prevention and infection control in the dialysis facilities were summarized. Leadership, education, preparedness, management, and recovery phase were determined to be the critical procedures. It is hoped this updated interim review might provide information for medical professionals to take proactive action to best prepare and mitigate damage when facing the COVID-19 pandemic challenge.

Thrombocytopenia, anasarca, and renal insufficiency as severe and rare complications of Hodgkin lymphoma: a case report.

BACKGROUND: Patients with Hodgkin lymphoma exhibit various clinical presentations. Needle biopsy of the lymph nodes is a minimally invasive procedure and a useful diagnostic method for malignant lymphomas. However, at times it is difficult to differentiate malignant lymphomas from reactive lymph node changes using a small amount of biopsy material. CASE PRESENTATION: A 77-year-old Japanese man was referred to the emergency department of our hospital owing to high fever and disturbance of consciousness. We diagnosed sepsis due to an acute biliary tract infection because he presented with Charcot's triad-fever, jaundice, and right-sided abdominal pain. However, he did not respond well to antimicrobial therapy and his high fever persisted. Considering the swelling of the right cervical, mediastinal, and intraperitoneal lymph nodes and splenomegaly detected on computed tomography, a differential diagnosis of malignant lymphoma was needed. Hence, we performed a needle biopsy of the right cervical lymph node; however, the amount of sample obtained was insufficient in establishing a definitive diagnosis of malignant lymphoma. Furthermore, during hospitalization, the patient developed thrombocytopenia, anasarca, and renal insufficiency. These symptoms seemed to be the typical signs of the thrombocytopenia, anasarca, fever, reticulin fibrosis or renal insufficiency, and organomegaly syndrome. Next, an external incisional mass biopsy of the right cervical lymph node was performed, which helped identify Hodgkin and Reed-Sternberg cells. Collectively, we established a definitive diagnosis of Hodgkin lymphoma with lymphoma-associated hemophagocytic syndrome. CONCLUSIONS: This case highlights the importance of performing an external incisional mass biopsy of the lymph nodes for the early diagnosis and treatment, if malignant lymphoma is strongly suspected.

Leveraging Prior Healthy Participant Pharmacokinetic Data to Evaluate the Impact of Renal and Hepatic Impairment on Ritlecitinib Pharmacokinetics.

Ritlecitinib is a selective, covalent, irreversible inhibitor of Janus kinase 3 (JAK3) and the tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases. Pharmacokinetics and safety of ritlecitinib in participants with hepatic (Study 1) or renal (Study 2) impairment were to be characterized from two phase I studies. Due to a study pause caused by the COVID-19 pandemic, the study 2 healthy participant (HP) cohort was not recruited; however, the demography of the severe renal impairment cohort closely matched the study 1 HP cohort. We present results from each study and two innovative approaches to utilizing available HP data as reference data for study 2: a statistical approach using analysis of variance and an in silico simulation of an HP cohort created using a population pharmacokinetics (POPPK) model derived from several ritlecitinib studies. For study 1, the observed area under the curve for 24-h dosing interval and maximum plasma concentration for HPs and their observed geometric mean ratios (participants with moderate hepatic impairment vs HPs) were within 90% prediction intervals from the POPPK simulation-based approach, thereby validating the latter approach. When applied to study 2, both the statistical and POPPK simulation approaches demonstrated that patients with renal impairment would not require ritlecitinib dose modification. In both phase I studies, ritlecitinib was generally safe and well tolerated. These analyses represent a new methodology for generating reference HP cohorts in special population studies for drugs in development with well-characterized pharmacokinetics in HPs and adequate POPPK models. TRIAL REGISTRATION: ClinicalTrials.gov NCT04037865 , NCT04016077 , NCT02309827 , NCT02684760 , and NCT02969044 .

Effect of remdesivir on adverse kidney outcomes in hospitalized patients with COVID-19 and impaired kidney function.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for mortality from COVID-19. Remdesivir has been shown to shorten time to recovery in patients with severe COVID-19. However, exclusion of patients with severe kidney function impairment in clinical trials has led to concerns about kidney safety of remdesivir in patients with pre-existing kidney disease. METHODS: Retrospective propensity score matched cohort study of hospitalized patients with COVID-19 admitted with estimated glomerular filtration rate (eGFR) between 15 - 60 mL/min/1.73m2. Remdesivir-treated patients were 1:1 matched to historical comparators admitted during the first wave of COVID-19 (between March-April 2020) prior to emergency use authorization of remdesivir using propensity scores accounting for factors predicting treatment assignment. Dependent outcomes included in-hospital peak creatinine, incidence of doubling of creatine, rate of kidney replacement therapy initiation and eGFR among surviving patients at day 90. RESULTS: 175 remdesivir-treated patients were 1:1 matched to untreated historical comparators. Mean age was 74.1 (SD 12.8), 56.9% were male, 59% patients were white, and the majority (83.1%) had at least one co-morbidity. There were no statistically significant differences in peak creatinine during hospitalization (2.3mg/dL vs. 2.5 mg/dL, P = 0.34), incidence of doubling of creatinine (10.3% vs. 13.1%, P = 0.48), and rate of kidney replacement therapy initiation (4.6% vs. 6.3%, P = 0.49) in remdesivir-treated patients versus matched untreated historical comparators, respectively. Among surviving patients, there was no difference of the average eGFR at day 90 (54.7 ± 20.0 mL/min/1.73m2 for remdesivir-treated patients vs. 51.7 ± 19.5 mL/min/1.73m2 for untreated comparators, P = 0.41). CONCLUSIONS: Remdesivir use in patients with impaired kidney function (eGFR between 15 - 60 mL/min/1.73m2) who present to the hospital with COVID-19 is not associated with increased risk of adverse kidney outcomes.

The role of ECMO in COVID-19 acute respiratory failure: Defining risk factors for mortality.

BACKGROUND: Veno-venous extracorporeal membrane oxygenation (VV ECMO) utilization increased substantially during the COVID-19 pandemic, but without patient selection criteria. METHODS: We conducted a retrospective review of all adult patients with COVID-19-associated ARDS placed on VV ECMO at our institution from April 2020 through June 2022. RESULTS: 162 patients were included (n = 95 Pre-Delta; n = 58 Delta; n = 9 Omicron). The frequency of ECMO duration greater than three weeks was variable by pandemic period (17% pre-Delta, 41% Delta, 22% Omicron, p = 0.003). In-hospital mortality was 60.5%. Age ≥50 years (RR 1.28, 95% CI 1.01, 1.62), ≥7 days of respiratory support (1.39, 95% CI 1.05, 1.83) and pre-cannulation renal failure requiring dialysis (RR 1.42, 95% CI 1.13, 1.78) were associated with mortality. CONCLUSIONS: In this cohort of VV ECMO patients with COVID-19, older age, a longer duration of pre-ECMO respiratory support, and pre-ECMO renal failure all increased the risk of mortality by approximately 30%.

Growing a peritoneal dialysis program in Palestine from zero to 178 patients in 5 years: a single-center experience.

INTRODUCTION: Kidney failure is rapidly rising in Palestine, as the number of patients receiving maintenance dialysis has quadrupled in the last 15 years. In this study, we share an overview of our experience growing a peritoneal dialysis (PD) program from zero to 178 patients in 5 years at An-Najah National University Hospital in Palestine, presenting some challenges and ways to overcome them. METHODS: This was a single-center retrospective study of patients treated with PD from November 2016 to December 2021. Demographic and clinical data were obtained for each patient. In addition, PD discontinuation, peritonitis, and mortality rates were calculated and presented as the primary patient outcomes. RESULTS: A total of 158 patients were eligible for the study. The mean age was 51.8 ± 16.4 years, and 53.8% of patients were male. Diabetic nephropathy was the most common cause of kidney failure. 63 episodes of peritonitis were diagnosed in 48 patients (30.4%) for a rate of 1 episode/ 38.2 patient-months (0.31 episodes/ patient-years). 20 patients had their PD treatment discontinued, mainly due to psychosocial reasons and infectious and mechanical complications. Death was the fate of 27 patients, with cardiovascular disease and COVID-19 being the two main causes. CONCLUSION: The outcomes of this experience proved favorable and showed that PD could serve as a viable option for kidney failure patients in Palestine. Moreover, this study can serve as an example for other places where circumstances are challenging to take the initiative of starting their PD programs.

Diffuse proliferative glomerulonephritis in a patient with COVID-19 infection.

COVID-19 primarily presents with respiratory involvement. Extrapulmonary manifestations as the sole manifestation also occur although rare. The kidney, being one of the organs with the greatest number of ACE receptors, is usually reported as part of multiorgan involvement. We report an early adolescent boy who presented with nephrotic-nephritic syndrome with severe kidney dysfunction from COVID-19 infection. He had low C3 and undetected antineutrophil cytoplasmic antibodies, antinuclear antibody and antistreptolysin O. Kidney biopsy revealed findings consistent with diffuse proliferative glomerulonephritis with a focal glomerular crescent formation and thin basement nephropathy. Due to the rapidly progressive deterioration of kidney function, he was given pulse methylprednisolone therapy followed by oral prednisone. Complete recovery was documented 12 weeks after the onset of post-infectious glomerulonephritis. The possible pathogenesis of glomerulonephritis in a patient with COVID-19, its differential diagnosis and treatment are discussed.

Spontaneous pneumomediastinum in a COVID-19 patient after renal transplantation: a case report and literature review (preprint)

Background: Spontaneous pneumomediastinum is a rare complication in COVID-19. Severe pneumonia complicated with pneumomediastinum after renal transplantation is rarely reported. Here we report a case of pneumomediastinum before invasive mechanical ventilation (IMV) in a COVID-19 patient with long-term immunosuppressive therapy after renal transplantation. Case presentation: A 57-year-old man was admitted to our center with the main complaint of “fever and dyspnea for 5 days”. His past medical history was notable for renal transplantation and with long-term immunosuppressive and anti-rejection therapy. We made the diagnosis as COVID-19 pneumonia (severe type). We managed the patient with high flow nasal cannulae (HFNC), oral dexamethasone, broad-spectrum antibiotic, prophylactic anticoagulation, and anti-viral therapy with reduced dose of azvudine due to severe renal insufficiency. During hospitalization, the patient suffered from several times of aggravation of dyspnea. First bedside chest X-ray showed suspicious pneumomediastinum and subcutaneous emphysema, and the gas in the mediastinum gradually increased. The patient’s status deteriorated rapidly, we performed urgent trachea intubation and mechanical ventilation with low tidal volume lung-protective model and performed mediastinal decompression by suprasternal drainage. Despite our active rescue efforts, the patient still died of severe infection and multiple organ failure. Conclusions: In conclusion, we are the first to report spontaneous pneumomediastinum in a renal transplant recipient with severe COVID-19 pneumonia. This case reminds us that pneumomediastinum is a severe complication and a poor prognostic factor of COVID-19 pneumonia, especially when it occurred without positive pressure ventilation and in immunocompromised patients.

Decreased serum vitamin D level as a prognostic marker in patients with COVID-19 (preprint)

Background: The corona virus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2, is still localized outbreak and has resulted in a high rate of infection and severe disease in older patients with comorbidities. The vitamin D status of the population has been found to be an important factor that could influence outcome of COVID-19. However, whether vitamin D can lessen the symptoms or severity of COVID-19 still remains controversial. Methods: A total of 719 patients with confirmed COVID-19 were enrolled retrospectively in this study from April 13 to June 6, 2022 at Shanghai Forth People's Hospital. The circulating levels of 25(OH)D3, inflammatory factors, and clinical parameters were assayed. Time to viral RNA clearance (TVRC), classification and prognosis of COVID-19 were used to evaluate the severity of COVID-19 infection. Results: The median age was 76 years (interquartile range, IQR, 64.5-84.6), 44.1% of patients were male, and the TVRC was 11 days (IQR, 7-16) in this population. The median level of 25(OH)D3 was 27.15 (IQR, 19.31-38.89) nmol/L. Patients with lower serum 25(OH)D3 had prolonged time to viral clearance, more obvious inflammatory response, more severe respiratory symptoms and higher risks of impaired hepatic and renal function. Multiple regression analyses revealed that serum 25(OH)D3 level was negatively associated with TVRC independently. ROC curve showed the serum vitamin D level could predict the severity classification and prognosis of COVID-19 significantly.Conclusions: Serum 25(OH)D3 level is independently associated with the severity of COVID-19 in elderly, and it could be used as a predictor of the severity of COVID-19. In addition, supplementation with vitamin D might provide beneficial effects in old patients with COVID-19.

A Variant Mutation in the gene encoding Mitochondrial Seryl-tRNA Synthetase Cause HUPRA Syndrome with Atypical Presentation-A Case Report (preprint)

Background Hyperuricemia, pulmonary hypertension, renal failure, and alkaline intoxication syndrome (HUPRA syndrome) is a rare autosomal recessive mitochondrial disease with prevalence of less than one in a million. Due to mutations in the mitochondrial SARS enzyme encoding seryl-tRNA synthetase on chromosome 19 (19q13.2). Case–Diagnosis/Treatment We investigated two Palestinian girls from the same village presented with progressive renal failure in infancy were diagnosed with this multisystemic disease. presented with atypical clinical manifestations of HUPRA syndrome include leukopenia, anemia, salt wasting resulting in hyponatremia and hypochloremia, renal failure with elevated blood lactate, marked hyperuricemia, hypercholesterolemia and hypertriglyceridemia but  without  pulmonary hypertension or alkaline intoxication that distinguish them from the rest of the usual cases, instead they showed acidosis in routine follow up. By using single exome sequencing analysis, we identified a two homozygous pathogenic mutation c.1175A>G (p.D392G), c.1169A>G (D390G) in SARS2 gene. This sequence identified a new variant mutation of HUPRA syndrome c.1175A>G (p.D392G) with atypical presentation, that will be added to the literature. Conclusion SARS2 gene with pathogenic homozygous mutation variants were detected in our two patients c.1175A>G (p.D392G), c.1169A>G (D390G) in exon 13, with atypical clinical manifestations of HUPRA syndrome, expanding the spectrum of SARS2 pathogenic variants with its characteristic findings, describing the differences in clinical manifestations between homozygous and compound heterozygous mutations.

Growing a Peritoneal Dialysis Program in Palestine from Zero to 178 Patients in 5 Years: A Single-Center Experience (preprint)

Introduction: Kidney failure is rapidly rising in Palestine, as the number of patients receiving maintenance dialysis has quadrupled in the last 15 years. In this study, we share an overview of our experience growing a peritoneal dialysis (PD) program from zero to 178 patients in five years at An-Najah National University Hospital in Palestine, presenting some challenges and ways to overcome them. Methods: This was a single-center retrospective study of patients treated with PD from November 2016 to December 2021. Demographic and clinical data were obtained for each patient. In addition, PD discontinuation, peritonitis, and mortality rates were calculated and presented as the primary patient outcomes. Results: A total of 158 patients were eligible for the study. The mean age was 51.8 ± 16.4 years, and 53.8% of patients were male. Diabetic nephropathy was the most common cause of kidney failure. Sixty-three episodes of peritonitis were diagnosed in 48 patients (30.4%) for a rate of 1 episode/ 38.2 patient-months (0.31 episodes/ patient-years). Twenty patients had their PD treatment discontinued, mainly due to psychosocial reasons and infectious and mechanical complications. Death was the fate of 27 patients, with cardiovascular disease and COVID-19 being the two main causes. Conclusion: The outcomes of this experience proved favorable and showed that PD could serve as a viable option for kidney failure patients in Palestine. Moreover, this study can serve as an example for other places where circumstances are challenging to take the initiative of starting their PD programs.

Cytokine and Chemokine Retention Profile in COVID-19 Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) patients are more susceptible to infections compared to the general population. SARS-CoV-2 virus pathology is characterized by a cytokine storm responsible for the systemic inflammation typical of the COVID-19 disease. Since CKD patients have a reduced renal clearance, we decided to investigate whether they accumulate harmful mediators during the COVID-19 disease. We conducted a retrospective study on 77 COVID-19 hospitalized subjects in the acute phase of the illness. Thirteen different cytokines were assessed in plasma collected upon hospitalization. The patients were divided into three groups according to their estimated glomerular filtration rate, eGFR &lt; 30 (n = 23), 30 &lt; eGFR &lt; 60 (n = 33), eGFR &gt; 60 mL/min (n = 21). We found that Tumor Necrosis Factor α and its receptors I and II, Interleukin-7, Leukemia Inhibitory Factor, FAS receptor, Chitinase 3-like I, and the Vascular Endothelial Growth Factor showed an increased accumulation that negatively correlate with eGFR. Moreover, non-survivor patients with an impaired kidney function have significantly more elevated levels of the same mediators. In conclusion, there is a tendency in COVID-19 ESRD patients to accumulate harmful cytokines. The accumulation seems to associate with mortality outcomes and may be due to reduced clearance but also to increased biosynthesis in most severe cases.