Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

Acute kidney injury in patients treated with immune checkpoint inhibitors

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

Haemorrhagic peritonitis as a late complication of echocardiography guided pericardiocentesis

Clinically significant pericardial effusion is an uncommon complication after cardiac surgery. Pericardiocentesis can be performed either through a mini-sternotomy or under echocardiography guidance. Echocardiography guidance is a relatively safe procedure and it avoids the need for another general anaesthetic. However, in this post cardiac surgical patient echocardiography guided pericardiocentesis was complicated several days later by haemorrhagic peritonitis

Variation in the active compounds among natural populations of Swertia cordata

Swertia cordata (Wall. ex G. Don) C.B. Clarke is an important medicinal plant of the family Gentianaceae and is found distributed throughout temperate regions of the Himalaya. The species is used in various ethno-medicinal systems and as an adulterant of Swertia chirayita. Plants collected during the flowering stage from four different populations were air dried and crushed to make extract. The extract was analyzed using HPLC for the presence of bioactive molecules. Quantitative variations exist in the bioactive compounds among different populations. Variations among studied populations are due to long term adaptation in particular ecological niche. As S. chirayita has been banned for collection due to rarity in natural populations, S. cordata may be used as an alternate source. Presence of amarogentin, amaroswerin, and mangiferin increases the medicinal importance along with further research on chemistry, pharmacology, domestication, and crop improvement aspects of S. cordata

Variation in the active compounds among natural populations of <em>Swertia cordata</em>

224-229Swertia cordata (Wall. ex G. Don) C.B. Clarke is an important medicinal plant of the family Gentianaceae and is found distributed throughout temperate regions of the Himalaya. The species is used in various ethno-medicinal systems and as an adulterant of Swertia chirayita. Plants collected during the flowering stage from four different populations were air dried and crushed to make extract. The extract was analyzed using HPLC for the presence of bioactive molecules. Quantitative variations exist in the bioactive compounds among different populations. Variations among studied populations are due to long term adaptation in particular ecological niche. As S. chirayita has been banned for collection due to rarity in natural populations, S. cordata may be used as an alternate source. Presence of amarogentin, amaroswerin, and mangiferin increases the medicinal importance along with further research on chemistry, pharmacology, domestication, and crop improvement aspects of S. cordata

Development, micropropagation and characterization of colchiploid of <i>Echinacea</i><i> purpurea </i>(L.) Moench

221-224 To enhance the genetic resource base of Echinacea purpurea (L.) Moench, a tetraploid was developed by treating seeds with different concentrations of colchicine. For further multiplication, in vitro micropropagation through adventitious shoot induction and proliferation was achieved. Shoot buds were induced directly on adaxial surface of mature leaf tissues growing on MS medium supplemented with equimolar concentration of BAP and IBA. The optimum initial shoot regeneration frequency (63%) with average 2.3 shoots per explant was achieved after 30 d of culture initiation.  Maximum shoot organogenesis, with 8-10 shoots per culture flask, was obtained on the same medium after 10th subculture. Proliferating callus with intermixed shoot buds was derived from leaf tissue explants placed on MS medium supplemented with 1 mg L-1 each of BAP and IAA. The regenerated shoots were rooted on MS medium devoid of any growth regulator. Rooted plantlets were hardened under greenhouse conditions at 20-22°C with 85-90% RH. About 95% plantlets survived acclimatization, producing phenotypically normal plants in the greenhouse. After 4 wks, rooted plants were successfully transferred to soil in experimental field station at Jammu. Comparable field trials were laid with parental diploids. Tetraploids were dwarf, showed low seed set but were superior because of higher caffeic acid content. The results of this study have established a procedure for development and propagation of tetraploid of E. purpurea having higher caffeic acid content.</smarttagtype

Podophyllum lignans array of Podophyllum hexandrum Royle populations from semi-desert alpine region of Zanskar valley in Himalayas

Podophyllum hexandrum Royle (Syn. P. emodi Wale) a perennial rhizomatous herb found in alpine region distributed in the entire range of Himalayas from Ladakh to Sikkim at an altitude of 3000–4200masl is an preferred commercial source of Podophyllum lignans. It contains three times more Podophyllotoxin than the American species, Podophyllum peltatum. The present study was aimed to investigate variation of Podophyllum lignans contents based on six marker compounds viz. Podophyllotoxin; Deoxypodophyllotoxin;Picropodophyllotoxin; Podophyllotoxin �-d-glucopyanoside; Isopicropodophyllone; 4�-Demethyldeoxypodophyllotoxin, �-d-lucopyanoside, in P. hexandrum population growing at three locations. Further, ontogenetic and morphogenetic variations of Podophyllum lignan contents were studied to investigate dynamics of accumulation of these compounds. Representative collections from three locations viz., Panikhar, Padam and Tangoli located in Trans Himalayan semi-desert region of Zanskar valley were harvested at three stages (dormancy, active growth and maturity). Plants were dissected into root, rhizome and rhizome-buds, dried separately and assayed for Podophyllum lignan contents by high performance liquid chromatography

4-epi-Pimaric acid: a phytomolecule as a potent antibacterial and anti-biofilm agent for oral cavity pathogens

The present study focused on the antibacterial and biofilm inhibitory potential of 4-epi-pimaric acid isolated from aerial parts (stem and leaves) of Aralia cachemirica L. (Araliaceae) against oral cavity pathogens. 4-epi-Pimaric acid exhibited minimum inhibitory concentration (MIC) in the range of 4–16 μg/ml and minimum bactericidal concentration (MBC) two- to four-folds higher than MIC. There was significant inhibition in the biofilm formation by Streptococcus mutans on the saliva coated surface (P<0.05), and confocal microscopy revealed that 4-epi-pimaric acid inhibited the clumping and attachment of S. mutans. At 8×MIC concentration, it significantly prevented the pH drop and reduced S. mutans biofilms (P<0.05). Increased propidium iodide staining and leakage of 260- and 280-nm absorbing material by 4-epi-pimari