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Impact of Angiotensin Receptor-Neprilysin Inhibition Combined with Enteral Nutritional Therapy on Cardiac Performance and Inflammatory Burden in Hemodialysis-Associated Heart Failure: Clinical and Experimental Evidence.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Impact of Angiotensin Receptor-Neprilysin Inhibition Combined with Enteral Nutritional Therapy on Cardiac Performance and Inflammatory Burden in Hemodialysis-Associated Heart Failure: Clinical and Experimental Evidence.
Συγγραφείς: Liu X; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China., Lu T; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China., Hu Q; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China., Yang C; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China.
Πηγή: Malawi medical journal : the journal of Medical Association of Malawi [Malawi Med J] 2026 Jul 22; Vol. 38 (2), pp. 94-101. Date of Electronic Publication: 2026 Jul 22 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article; Randomized Controlled Trial
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Published by Montfort Press for the Medical Association of Malawi Country of Publication: Malawi NLM ID: 9500170 Publication Model: eCollection Cited Medium: Internet ISSN: 1995-7270 (Electronic) Linking ISSN: 19957262 NLM ISO Abbreviation: Malawi Med J Subsets: MEDLINE
Imprint Name(s): Original Publication: Lilongwe, Malawi : Published by Montfort Press for the Medical Association of Malawi, [1990-
Ιατρικοί όροι (MeSH): Heart Failure*/therapy , Heart Failure*/etiology , Heart Failure*/drug therapy , Heart Failure*/physiopathology , Enteral Nutrition*/methods , Aminobutyrates*/therapeutic use , Neprilysin*/antagonists & inhibitors , Renal Dialysis*/adverse effects , Angiotensin Receptor Antagonists*/therapeutic use , Tetrazoles*/therapeutic use, Valsartan/therapeutic use ; Biomarkers/blood ; Kidney Failure, Chronic/therapy ; Humans ; Male ; Biphenyl Compounds ; Female ; Animals ; Drug Combinations ; Middle Aged ; Rats ; Quality of Life ; Aged ; Treatment Outcome ; Inflammation
Περίληψη: Background: Cardiovascular complications remain the leading cause of mortality in patients undergoing maintenance hemodialysis (MHD), with heart failure (HF) representing a major clinical challenge. Beyond neurohormonal dysregulation, malnutrition and chronic microinflammation contribute significantly to disease progression. This study investigated whether angiotensin receptor-neprilysin inhibition combined with enteral nutritional support could provide additive benefits in this high-risk population.
Methods: A randomized controlled clinical study was conducted involving 60 MHD patients with HF, allocated to standard therapy or combined intervention groups. The intervention consisted of sacubitril/valsartan administration together with structured enteral nutrition support. Cardiac structure and function, inflammatory markers, nutritional indices, immune parameters, and quality-of-life scores were evaluated over 6 months. In parallel, a rat model of post-infarction HF was established to validate mechanistic and physiological changes, including echocardiographic measurements and serum biomarker assessment.
Results: Patients receiving the combined regimen demonstrated superior improvement in left ventricular systolic performance, with greater reductions in LV dimensions and circulating BNP levels compared with conventional treatment. Inflammatory mediators including IL-1β, IL-6, and CRP were significantly attenuated, while serum albumin, total protein, hemoglobin, and immunoglobulin levels increased more prominently. Quality-of-life scores improved without excess adverse events. Experimental findings mirrored clinical observations: treated rats exhibited improved LVEF, reduced ventricular remodeling indices, and decreased BNP and pro-inflammatory cytokines relative to untreated HF controls.
Conclusion: The integration of sacubitril/valsartan therapy with enteral nutritional supplementation exerts synergistic effects on cardiac remodeling, inflammatory modulation, and metabolic recovery in MHD-associated HF. These findings support a multidimensional therapeutic strategy targeting both neurohormonal activation and nutritional-inflammatory imbalance.
(© 2026 Kamuzu University of Health Sciences.)
Competing Interests: The authors declare that they have no competing interests. Disclosure of potential conflicts has been considered per MMJ instructions.
References: JPEN J Parenter Enteral Nutr. 2015 Feb;39(2):154-62. (PMID: 24096266)
Nephrol Dial Transplant. 2023 Jul 31;38(8):1880-1889. (PMID: 36787894)
J Am Coll Cardiol. 2021 May 11;77(18):2307-2319. (PMID: 33958128)
Ren Fail. 2017 Nov;39(1):153-158. (PMID: 27846790)
Eur Heart J. 2021 Sep 21;42(36):3741-3752. (PMID: 34392331)
Nat Rev Cardiol. 2020 May;17(5):269-285. (PMID: 31969688)
Pak J Med Sci. 2022 Jan-Feb;38(1):302-309. (PMID: 35035444)
JAMA. 2019 Sep 17;322(11):1085-1095. (PMID: 31475295)
J Am Geriatr Soc. 2023 Nov;71(11):3354-3356. (PMID: 37707391)
Circ Arrhythm Electrophysiol. 2024 May;17(5):e012517. (PMID: 38666379)
ESC Heart Fail. 2020 Jun;7(3):1125-1129. (PMID: 32153122)
Medicine (Baltimore). 2021 May 14;100(19):e25891. (PMID: 34106645)
Front Cardiovasc Med. 2022 Nov 09;9:955780. (PMID: 36440034)
Hypertension. 2023 Jun;80(6):e112-e122. (PMID: 37092336)
J Am Coll Cardiol. 2019 Feb 26;73(7):807-809. (PMID: 30784674)
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019 Jul;31(7):903-905. (PMID: 31441419)
J Card Fail. 2018 Nov;24(11):773-782. (PMID: 30347271)
J Cardiol. 2023 Mar;81(3):283-291. (PMID: 36370995)
Blood Purif. 2022;51(3):270-279. (PMID: 34753147)
Circulation. 2020 Feb 4;141(5):352-361. (PMID: 31736342)
JACC Heart Fail. 2020 Oct;8(10):800-810. (PMID: 33004114)
Am J Clin Nutr. 2021 Mar 11;113(3):501-502. (PMID: 33515012)
Am J Kidney Dis. 2021 May;77(5):704-712. (PMID: 33010357)
Pediatr Crit Care Med. 2020 Mar;21(3):213-221. (PMID: 31577692)
Nutrients. 2013 Feb 21;5(2):608-23. (PMID: 23429491)
J Am Geriatr Soc. 2023 Nov;71(11):3367-3375. (PMID: 37706670)
Clin Interv Aging. 2018 Mar 07;13:397-401. (PMID: 29563779)
BMC Cardiovasc Disord. 2023 Jul 10;23(1):343. (PMID: 37430227)
Ren Fail. 2023;45(2):2255686. (PMID: 37732398)
JNMA J Nepal Med Assoc. 2022 Nov 02;60(255):931-934. (PMID: 36705169)
Nat Rev Nephrol. 2011 Sep 06;7(11):650-8. (PMID: 21894181)
Lancet Diabetes Endocrinol. 2017 May;5(5):333-340. (PMID: 28330649)
Exp Ther Med. 2013 Aug;6(2):532-536. (PMID: 24137221)
Contributed Indexing: Keywords: enteral nutrition; heart failure; maintenance hemodialysis; microinflammatory status; sacubitril/valsartan
Substance Nomenclature: 0 (Biphenyl Compounds)
80M03YXJ7I (Valsartan)
0 (Aminobutyrates)
WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination)
EC 3.4.24.11 (Neprilysin)
0 (Drug Combinations)
0 (Angiotensin Receptor Antagonists)
0 (Tetrazoles)
0 (Biomarkers)
Entry Date(s): Date Created: 20260814 Date Completed: 20260814 Latest Revision: 20260831
Update Code: 20260901
PubMed Central ID: PMC13459000
DOI: 10.4314/mmj.v38i2.6
PMID: 42597327
Βάση Δεδομένων: MEDLINE
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  Data: Impact of Angiotensin Receptor-Neprilysin Inhibition Combined with Enteral Nutritional Therapy on Cardiac Performance and Inflammatory Burden in Hemodialysis-Associated Heart Failure: Clinical and Experimental Evidence.
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  Data: <searchLink fieldCode="AU" term="%22Liu+X%22">Liu X</searchLink>; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China.<br /><searchLink fieldCode="AU" term="%22Lu+T%22">Lu T</searchLink>; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China.<br /><searchLink fieldCode="AU" term="%22Hu+Q%22">Hu Q</searchLink>; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China.<br /><searchLink fieldCode="AU" term="%22Yang+C%22">Yang C</searchLink>; Department of Nephrology, Changzhou Geriatric Hospital Affiliated to Soochow University, Changzhou NO. 7 People's Hospital, Changzhou, Jiangsu 213018, China.
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  Data: <searchLink fieldCode="JN" term="%229500170%22">Malawi medical journal : the journal of Medical Association of Malawi</searchLink> [Malawi Med J] 2026 Jul 22; Vol. 38 (2), pp. 94-101. <i>Date of Electronic Publication: </i>2026 Jul 22 (<i>Print Publication: </i>2026).
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  Data: <i>Original Publication</i>: Lilongwe, Malawi : Published by Montfort Press for the Medical Association of Malawi, [1990-
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  Data: <searchLink fieldCode="MM" term="%22Heart+Failure%22">Heart Failure*</searchLink>/<searchLink fieldCode="MM" term="%22Heart+Failure+therapy%22">therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Heart+Failure%22">Heart Failure*</searchLink>/<searchLink fieldCode="MM" term="%22Heart+Failure+etiology%22">etiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Heart+Failure%22">Heart Failure*</searchLink>/<searchLink fieldCode="MM" term="%22Heart+Failure+drug+therapy%22">drug therapy</searchLink> <br /><searchLink fieldCode="MM" term="%22Heart+Failure%22">Heart Failure*</searchLink>/<searchLink fieldCode="MM" term="%22Heart+Failure+physiopathology%22">physiopathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Enteral+Nutrition%22">Enteral Nutrition*</searchLink>/<searchLink fieldCode="MM" term="%22Enteral+Nutrition+methods%22">methods</searchLink> <br /><searchLink fieldCode="MM" term="%22Aminobutyrates%22">Aminobutyrates*</searchLink>/<searchLink fieldCode="MM" term="%22Aminobutyrates+therapeutic+use%22">therapeutic use</searchLink> <br /><searchLink fieldCode="MM" term="%22Neprilysin%22">Neprilysin*</searchLink>/<searchLink fieldCode="MM" term="%22Neprilysin+antagonists+%26+inhibitors%22">antagonists & inhibitors</searchLink> <br /><searchLink fieldCode="MM" term="%22Renal+Dialysis%22">Renal Dialysis*</searchLink>/<searchLink fieldCode="MM" term="%22Renal+Dialysis+adverse+effects%22">adverse effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Angiotensin+Receptor+Antagonists%22">Angiotensin Receptor Antagonists*</searchLink>/<searchLink fieldCode="MM" term="%22Angiotensin+Receptor+Antagonists+therapeutic+use%22">therapeutic use</searchLink> <br /><searchLink fieldCode="MM" term="%22Tetrazoles%22">Tetrazoles*</searchLink>/<searchLink fieldCode="MM" term="%22Tetrazoles+therapeutic+use%22">therapeutic use</searchLink><br /><searchLink fieldCode="MH" term="%22Valsartan%22">Valsartan</searchLink>/<searchLink fieldCode="MH" term="%22Valsartan+therapeutic+use%22">therapeutic use</searchLink> ; <searchLink fieldCode="MH" term="%22Biomarkers%22">Biomarkers</searchLink>/<searchLink fieldCode="MH" term="%22Biomarkers+blood%22">blood</searchLink> ; <searchLink fieldCode="MH" term="%22Kidney+Failure%2C+Chronic%22">Kidney Failure, Chronic</searchLink>/<searchLink fieldCode="MH" term="%22Kidney+Failure%2C+Chronic+therapy%22">therapy</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Biphenyl+Compounds%22">Biphenyl Compounds</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Drug+Combinations%22">Drug Combinations</searchLink> ; <searchLink fieldCode="MH" term="%22Middle+Aged%22">Middle Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Rats%22">Rats</searchLink> ; <searchLink fieldCode="MH" term="%22Quality+of+Life%22">Quality of Life</searchLink> ; <searchLink fieldCode="MH" term="%22Aged%22">Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Treatment+Outcome%22">Treatment Outcome</searchLink> ; <searchLink fieldCode="MH" term="%22Inflammation%22">Inflammation</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Cardiovascular complications remain the leading cause of mortality in patients undergoing maintenance hemodialysis (MHD), with heart failure (HF) representing a major clinical challenge. Beyond neurohormonal dysregulation, malnutrition and chronic microinflammation contribute significantly to disease progression. This study investigated whether angiotensin receptor-neprilysin inhibition combined with enteral nutritional support could provide additive benefits in this high-risk population.<br />Methods: A randomized controlled clinical study was conducted involving 60 MHD patients with HF, allocated to standard therapy or combined intervention groups. The intervention consisted of sacubitril/valsartan administration together with structured enteral nutrition support. Cardiac structure and function, inflammatory markers, nutritional indices, immune parameters, and quality-of-life scores were evaluated over 6 months. In parallel, a rat model of post-infarction HF was established to validate mechanistic and physiological changes, including echocardiographic measurements and serum biomarker assessment.<br />Results: Patients receiving the combined regimen demonstrated superior improvement in left ventricular systolic performance, with greater reductions in LV dimensions and circulating BNP levels compared with conventional treatment. Inflammatory mediators including IL-1β, IL-6, and CRP were significantly attenuated, while serum albumin, total protein, hemoglobin, and immunoglobulin levels increased more prominently. Quality-of-life scores improved without excess adverse events. Experimental findings mirrored clinical observations: treated rats exhibited improved LVEF, reduced ventricular remodeling indices, and decreased BNP and pro-inflammatory cytokines relative to untreated HF controls.<br />Conclusion: The integration of sacubitril/valsartan therapy with enteral nutritional supplementation exerts synergistic effects on cardiac remodeling, inflammatory modulation, and metabolic recovery in MHD-associated HF. These findings support a multidimensional therapeutic strategy targeting both neurohormonal activation and nutritional-inflammatory imbalance.<br /> (© 2026 Kamuzu University of Health Sciences.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: The authors declare that they have no competing interests. Disclosure of potential conflicts has been considered per MMJ instructions.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: JPEN J Parenter Enteral Nutr. 2015 Feb;39(2):154-62. (PMID: <searchLink fieldCode="PM" term="%2224096266%22">24096266)</searchLink><br />Nephrol Dial Transplant. 2023 Jul 31;38(8):1880-1889. (PMID: <searchLink fieldCode="PM" term="%2236787894%22">36787894)</searchLink><br />J Am Coll Cardiol. 2021 May 11;77(18):2307-2319. (PMID: <searchLink fieldCode="PM" term="%2233958128%22">33958128)</searchLink><br />Ren Fail. 2017 Nov;39(1):153-158. (PMID: <searchLink fieldCode="PM" term="%2227846790%22">27846790)</searchLink><br />Eur Heart J. 2021 Sep 21;42(36):3741-3752. (PMID: <searchLink fieldCode="PM" term="%2234392331%22">34392331)</searchLink><br />Nat Rev Cardiol. 2020 May;17(5):269-285. (PMID: <searchLink fieldCode="PM" term="%2231969688%22">31969688)</searchLink><br />Pak J Med Sci. 2022 Jan-Feb;38(1):302-309. (PMID: <searchLink fieldCode="PM" term="%2235035444%22">35035444)</searchLink><br />JAMA. 2019 Sep 17;322(11):1085-1095. (PMID: <searchLink fieldCode="PM" term="%2231475295%22">31475295)</searchLink><br />J Am Geriatr Soc. 2023 Nov;71(11):3354-3356. (PMID: <searchLink fieldCode="PM" term="%2237707391%22">37707391)</searchLink><br />Circ Arrhythm Electrophysiol. 2024 May;17(5):e012517. (PMID: <searchLink fieldCode="PM" term="%2238666379%22">38666379)</searchLink><br />ESC Heart Fail. 2020 Jun;7(3):1125-1129. (PMID: <searchLink fieldCode="PM" term="%2232153122%22">32153122)</searchLink><br />Medicine (Baltimore). 2021 May 14;100(19):e25891. (PMID: <searchLink fieldCode="PM" term="%2234106645%22">34106645)</searchLink><br />Front Cardiovasc Med. 2022 Nov 09;9:955780. (PMID: <searchLink fieldCode="PM" term="%2236440034%22">36440034)</searchLink><br />Hypertension. 2023 Jun;80(6):e112-e122. (PMID: <searchLink fieldCode="PM" term="%2237092336%22">37092336)</searchLink><br />J Am Coll Cardiol. 2019 Feb 26;73(7):807-809. (PMID: <searchLink fieldCode="PM" term="%2230784674%22">30784674)</searchLink><br />Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019 Jul;31(7):903-905. (PMID: <searchLink fieldCode="PM" term="%2231441419%22">31441419)</searchLink><br />J Card Fail. 2018 Nov;24(11):773-782. (PMID: <searchLink fieldCode="PM" term="%2230347271%22">30347271)</searchLink><br />J Cardiol. 2023 Mar;81(3):283-291. (PMID: <searchLink fieldCode="PM" term="%2236370995%22">36370995)</searchLink><br />Blood Purif. 2022;51(3):270-279. (PMID: <searchLink fieldCode="PM" term="%2234753147%22">34753147)</searchLink><br />Circulation. 2020 Feb 4;141(5):352-361. (PMID: <searchLink fieldCode="PM" term="%2231736342%22">31736342)</searchLink><br />JACC Heart Fail. 2020 Oct;8(10):800-810. (PMID: <searchLink fieldCode="PM" term="%2233004114%22">33004114)</searchLink><br />Am J Clin Nutr. 2021 Mar 11;113(3):501-502. (PMID: <searchLink fieldCode="PM" term="%2233515012%22">33515012)</searchLink><br />Am J Kidney Dis. 2021 May;77(5):704-712. (PMID: <searchLink fieldCode="PM" term="%2233010357%22">33010357)</searchLink><br />Pediatr Crit Care Med. 2020 Mar;21(3):213-221. (PMID: <searchLink fieldCode="PM" term="%2231577692%22">31577692)</searchLink><br />Nutrients. 2013 Feb 21;5(2):608-23. (PMID: <searchLink fieldCode="PM" term="%2223429491%22">23429491)</searchLink><br />J Am Geriatr Soc. 2023 Nov;71(11):3367-3375. (PMID: <searchLink fieldCode="PM" term="%2237706670%22">37706670)</searchLink><br />Clin Interv Aging. 2018 Mar 07;13:397-401. (PMID: <searchLink fieldCode="PM" term="%2229563779%22">29563779)</searchLink><br />BMC Cardiovasc Disord. 2023 Jul 10;23(1):343. (PMID: <searchLink fieldCode="PM" term="%2237430227%22">37430227)</searchLink><br />Ren Fail. 2023;45(2):2255686. (PMID: <searchLink fieldCode="PM" term="%2237732398%22">37732398)</searchLink><br />JNMA J Nepal Med Assoc. 2022 Nov 02;60(255):931-934. (PMID: <searchLink fieldCode="PM" term="%2236705169%22">36705169)</searchLink><br />Nat Rev Nephrol. 2011 Sep 06;7(11):650-8. (PMID: <searchLink fieldCode="PM" term="%2221894181%22">21894181)</searchLink><br />Lancet Diabetes Endocrinol. 2017 May;5(5):333-340. (PMID: <searchLink fieldCode="PM" term="%2228330649%22">28330649)</searchLink><br />Exp Ther Med. 2013 Aug;6(2):532-536. (PMID: <searchLink fieldCode="PM" term="%2224137221%22">24137221)</searchLink>
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  Data: <i>Keywords: </i>enteral nutrition; heart failure; maintenance hemodialysis; microinflammatory status; sacubitril/valsartan
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      – SubjectFull: Valsartan therapeutic use
        Type: general
      – SubjectFull: Biomarkers blood
        Type: general
      – SubjectFull: Kidney Failure, Chronic therapy
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      – SubjectFull: Heart Failure drug therapy
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      – SubjectFull: Aminobutyrates therapeutic use
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      – SubjectFull: Neprilysin antagonists & inhibitors
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      – SubjectFull: Angiotensin Receptor Antagonists therapeutic use
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      – TitleFull: Impact of Angiotensin Receptor-Neprilysin Inhibition Combined with Enteral Nutritional Therapy on Cardiac Performance and Inflammatory Burden in Hemodialysis-Associated Heart Failure: Clinical and Experimental Evidence.
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    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Liu X
      – PersonEntity:
          Name:
            NameFull: Lu T
      – PersonEntity:
          Name:
            NameFull: Hu Q
      – PersonEntity:
          Name:
            NameFull: Yang C
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 22
              M: 07
              Text: 2026 Jul 22
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1995-7270
          Numbering:
            – Type: volume
              Value: 38
            – Type: issue
              Value: 2
          Titles:
            – TitleFull: Malawi medical journal : the journal of Medical Association of Malawi
              Type: main
ResultId 1