Elevated tacrolimus levels among COVID-19 kidney transplant recipients are associated with worse disease severity and clinical outcomes.

BACKGROUND: The therapeutic effects of immunosuppressive drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections causing coronavirus disease 2019 (COVID-19) are being actively investigated. However, COVID-19's potential effects on serum calcineurin inhibitor levels have only been described recently. This study aimed to evaluate COVID-19's effect on tacrolimus levels in renal transplant recipients with moderate to severe symptoms and to assess their potential correlation with disease severity. MATERIALS AND METHODS: We retrospectively investigated 50 kidney transplant recipients with moderate to severe COVID-19. Their tacrolimus trough level on admission was compared to baseline levels, and their laboratory measurements and clinical course were reviewed on days 1 (admission), 7, 14, and 28. RESULTS: We found that 90% of patients had admission tacrolimus trough levels above baseline, with a mean increase of 176%. In addition, 71% had tacrolimus trough levels ≥ 50% above baseline, and 40% had supra-therapeutic trough levels of > 15 ng/mL. Supra-therapeutic trough levels were associated with greater hypoxemic respiratory failure, acute kidney injury, and increased 30-day mortality. CONCLUSION: Elevated tacrolimus levels occur in many renal transplant recipients with moderate to severe COVID-19 and are associated with worse clinical outcomes. Close drug monitoring is crucial to avoid toxicities and minimize over-immunosuppression complications.

Ocular and Neuro-ophthalmic Manifestations Post COVID-19 Infection.

A 39-year-old male with a history of COVID-19 infection presented with ocular manifestations: dendritic ulcer in the left eye cornea followed by diplopia in the same eye. Extraocular motility was restricted in the levo-lateral gaze with maximum diplopia measuring 25∆ exotropia. Slit lamp biomicroscopy showed dendritic patterned lesion with diffused superficial punctate keratitis in the cornea. There are various reports associated with COVID-19 and the neuro-ophthalmic system. Although the clinicopathological aspect of COVID-19 and the neurological system is still to explicate. However, the patient showed gradual improvement with topical and systemic antiviral therapy and orthoptic exercise. This points to the need for detailed neurological and ophthalmic workup in symptomatic COVID-19 patients. Taking the risk of viral spread into serious consideration, a thorough evaluation is though mandatory. Keywords: COVID-19; dendritic ulcer; lateral rectus palsy; superficial punctate keratopathy.

Minimal change disease and COVID-19 vaccination: Four cases and review of literature.

There have been multiple reports of the development of de novo or relapse of glomerular diseases after SARS-CoV-2 vaccination. While most of them have occurred with the mRNA vaccines (Pfizer/BioNTech and Moderna/NIAID), there also have been reports associated with the vector vaccines (AstraZeneca/ChAdOx1-S) vaccine and the inactivated vaccines. Minimal change disease (MCD) is one of the more common glomerular diseases noted to have been associated with the COVID-19 vaccination. We report here 4 more cases of MCD occurring in association with the COVID-19 vaccine, 3 were de novo cases, and 1 case had a relapse of MCD. We also review all the 41 cases described thus far in the literature and review potential common pathways activated by the vaccination that play a role in the pathogenesis of MCD.

Evaluation of dry eye symptoms in lecturers working in medical colleges of Nepal: An online cross-sectional study following SARS-CoV-2 outbreak.

INTRODUCTION: Dry eye is one of the frequently encountered ophthalmological disorders. Following the pandemic of Coronavirus disease 2019, use of masks and electronic devices has taken an upraise globally. These factors are one of the causes for dry eye disease. This study emphasises dry eye symptoms among lecturers working in medical colleges of Nepal. MATERIALS AND METHODS: This was a descriptive cross sectional study conducted among 217 lecturers working in various medical colleges in Nepal. Dry eye evaluation was done using the Ocular Surface Disease Index (OSDI) questionnaire. Analysis of data was using Microsoft Excel 2016 and IBM Statistical Package for Social Sciences (SPSS) version 26.0. RESULTS: One fourth (25.80%) of 217 participants experienced symptoms of dry eye disease. CONCLUSION: Increasing use of mask and laptop during this pandemic era has shown to cause mild dry eye symptoms in lecturers working in medical colleges of Nepal. Proper care and precaution needs to be practised in order to minimise dry eye symptoms and its consequences.

Serum sickness induced by alemtuzumab in a kidney-pancreas transplant recipient.

Serum sickness is an immune-complex-mediated hypersensitivity reaction that was first noted in the early 1900s in patients receiving heterologous antisera, such as horse antitetanus or antidiphtheria serum. This condition is primarily self-limited; however, in its acute state, it can cause severe symptoms of fever, rash, polyarthritis, or polyarthralgias. In solid organ transplantation, this condition is frequently reported in association with the use of rabbit anti-thymocyte globulin and chimeric murine monoclonal antibodies such as rituximab. Alemtuzumab, designed as a humanized monoclonal antibody against CD52, is expected to be less immunogenic. Here, we report a case of serum sickness associated with alemtuzumab induction therapy in a kidney-pancreas dual-organ recipient.

Comparative Study of Dry Eye Indices Following Cataract Surgery.

BACKGROUND: This study aims to assess dry eye indices following cataract surgery. MATERIALS AND METHODS: A single center descriptive and comparative study was performed. A total of 100 eyes of 100 cases fulfilling the inclusion criteria from 1st June 2017 to 30th May 2018 were enrolled. Out of 100 eyes, 50 eyes each went through manual small incision cataract surgery (MSICS) and phacoemulsification respectively. For objective analysis : schirmer 1 test(ST-I), tear breakup Time(TBUT) along with lissamine Green Surface Staining(LGSS) was performed on pre-operative day, 1st, 4th and 12th week respectively. Ocular Surface Disease Index (OSDI) was done for subjective analysis on pre-operative day and at 12th week. RESULTS: The mean age of the patient was 53.66 ± 7.839 years with 34 (68%) being female in a small incision cataract surgery group. In the phacoemulsification group, mean age was 54.72 ± 7.985 years and 32 (64%) were female. On analyzing the objective dry eye indices: ST-I,TBUT and LGSS at 12thweek was 18.80 ± 7.393 mm, 11.30 ± 5.456 seconds and 1.62 ± 1.193 in Small incision cataract surgery group and 27.10 ± 6.326 mm, 16.60 ± 4.699 seconds and 0.38 ± 0.602 in Phacoemulsification group respectively which was statistically significant. (p< 0.001). CONCLUSION: Regardless of the type of cataract surgery, dry eye disease is unavoidable affecting both tear quality and quantity postoperatively. In our study, phacoemulsification had lesser effect in dry eye indices than small incision cataract surgery.

The role of procurement biopsies in acceptance decisions for kidneys retrieved for transplant.

BACKGROUND AND OBJECTIVES: There is a shortage of kidneys for transplant, and many patients on the deceased donor kidney transplant waiting list would likely benefit from kidneys that are currently being discarded. In the United States, the most common reason given for discarding kidneys retrieved for transplant is procurement biopsy results. This study aimed to compare biopsy results from discarded kidneys with discard attributed to biopsy findings, with biopsy results from comparable kidneys that were successfully transplanted. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective, observational, case-control study, biopsy reports were examined from 83 kidneys discarded in 2010 due to biopsy findings (cases), 83 contralateral transplanted kidneys from the same donor (contralateral controls), and 83 deceased donors randomly matched to cases by donor risk profile (randomly matched controls). A second procurement biopsy was obtained in 64 of 332 kidneys (19.3%). RESULTS: The quality of biopsy reports was low, with amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, and acute tubular necrosis often not indicated; 69% were wedge biopsies and 94% used frozen tissue. The correlation between first and second procurement biopsies was poor; only 25% of the variability (R(2)) in glomerulosclerosis was explained by biopsies being from the same kidney. The percentages of glomerulosclerosis overlapped substantially between cases, contralateral controls, and randomly matched controls: 17.1%±15.3%, 9.0%±6.6%, and 5.0%±5.9%, respectively. Of all biopsy findings, only glomerulosclerosis>20% was independently correlated with discard (cases versus contralateral controls; odds ratio, 15.09; 95% confidence interval, 2.47 to 92.41; P=0.003), suggesting that only this biopsy result was used in acceptance decisions. One-year graft survival was 79.5% and 90.7% in contralateral and randomly matched controls, respectively, versus 91.6% among all deceased donor transplants in the Scientific Registry of Transplant Recipients. CONCLUSIONS: Routine use of biopsies could lead to unnecessary kidney discards.

Development of a loop-mediated isothermal amplification assay for rapid detection of BK virus.

Loop-mediated isothermal amplification (LAMP) is a novel method for rapid amplification of DNA. Its advantages include rapidity and minimal equipment requirement. The LAMP assay was developed for BK virus (BKV), which is a leading cause of morbidity in renal transplant recipients. The characteristics of the assay, including its specificity and sensitivity, were evaluated. BKV LAMP was performed using various incubation times with a variety of specimens, including unprocessed urine and plasma samples. A ladder pattern on gel electrophoresis, typical of successful LAMP reactions, was observed specifically only for BKV and not for other viruses. The sensitivity of the assay with 1 h of incubation was 100 copies/tube of a cloned BKV fragment. Additionally, a positive reaction was visually ascertained by a simple color reaction using SYBR green dye. BKV LAMP was also successful for urine and plasma specimens without the need for DNA extraction. Due to its simplicity and specificity, the LAMP assay can potentially be developed for "point of care" screening of BKV.