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Abstract

Randomized Trial of Verubecestat for Prodromal Alzheimer\'s Disease.

Egan MF, Kost J, Voss T, Mukai Y, ... Sur C, Michelson D
Prodromal Alzheimer\'s disease offers an opportunity to test the effect of drugs that modify the deposition of amyloid in the brain before the onset of dementia. Verubecestat is an orally administered β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) inhibitor that blocks production of amyloid-beta (Aβ). The drug did not prevent clinical progression in a trial involving patients with mild-to-moderate dementia due to Alzheimer\'s disease.

N Engl J Med: 10 Apr 2019; 380:1408-1420
Egan MF, Kost J, Voss T, Mukai Y, ... Sur C, Michelson D
N Engl J Med: 10 Apr 2019; 380:1408-1420 | PMID: 30970186
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Impact:
Abstract

Colovesical Fistula.

Ashrafi AN, Sotelo R


N Engl J Med: 26 Jun 2019; 380:e51
Ashrafi AN, Sotelo R
N Engl J Med: 26 Jun 2019; 380:e51 | PMID: 31242365
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Impact:
Abstract

Liver Involvement in Autosomal Dominant Polycystic Kidney Disease.

Adin ME


N Engl J Med: 15 May 2019; 380:1954
Adin ME
N Engl J Med: 15 May 2019; 380:1954 | PMID: 31091376
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Impact:
Abstract

Question-Mark Appearance of the Colon.

Masiakos PT, Wales PW


N Engl J Med: 22 May 2019; 380:2051
Masiakos PT, Wales PW
N Engl J Med: 22 May 2019; 380:2051 | PMID: 31116921
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Impact:
Abstract

Case 11-2019: A 49-Year-Old Man with HIV Infection and Chronic Kidney Disease.

Wojciechowski D, Gandhi RT, Rosales IA


N Engl J Med: 10 Apr 2019; 380:1464-1472
Wojciechowski D, Gandhi RT, Rosales IA
N Engl J Med: 10 Apr 2019; 380:1464-1472 | PMID: 30970193
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Impact:
Abstract

(Pinworm) Infection.

Kang WH, Jee SC


N Engl J Med: 03 Jul 2019; 381:e1
Kang WH, Jee SC
N Engl J Med: 03 Jul 2019; 381:e1 | PMID: 31269369
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Impact:
Abstract

Case 14-2019: A 44-Year-Old Man with Neck Pain and Swelling.

Saylor PJ, Dudzinski DM, Mendoza DP, Glomski K


N Engl J Med: 08 May 2019; 380:1854-1863
Saylor PJ, Dudzinski DM, Mendoza DP, Glomski K
N Engl J Med: 08 May 2019; 380:1854-1863 | PMID: 31067377
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Impact:
Abstract

Tick Attached to the Tympanic Membrane.

Kasle D, Waldman E


N Engl J Med: 01 May 2019; 380:1761
Kasle D, Waldman E
N Engl J Med: 01 May 2019; 380:1761 | PMID: 31042828
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Impact:
Abstract

Nonnarcotic Methods of Pain Management.

Finnerup NB


N Engl J Med: 19 Jun 2019; 380:2440-2448
Finnerup NB
N Engl J Med: 19 Jun 2019; 380:2440-2448 | PMID: 31216399
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Impact:
Abstract

Case 15-2019: A 55-Year-Old Man with Jaundice.

Schaefer EA, Anderson MA, Kim AY, Sfeir MM


N Engl J Med: 15 May 2019; 380:1955-1963
Schaefer EA, Anderson MA, Kim AY, Sfeir MM
N Engl J Med: 15 May 2019; 380:1955-1963 | PMID: 31091378
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Impact:
Abstract

Intensive Glucose Control in Patients with Type 2 Diabetes - 15-Year Follow-up.

Reaven PD, Emanuele NV, Wiitala WL, Bahn GD, ... Hayward RA,
We previously reported that a median of 5.6 years of intensive as compared with standard glucose lowering in 1791 military veterans with type 2 diabetes resulted in a risk of major cardiovascular events that was significantly lower (by 17%) after a total of 10 years of combined intervention and observational follow-up. We now report the full 15-year follow-up.

N Engl J Med: 05 Jun 2019; 380:2215-2224
Reaven PD, Emanuele NV, Wiitala WL, Bahn GD, ... Hayward RA,
N Engl J Med: 05 Jun 2019; 380:2215-2224 | PMID: 31167051
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Impact:
Abstract

Tornwaldt\'s Cyst.

Huang CY, Kang BH


N Engl J Med: 15 May 2019; 380:e37
Huang CY, Kang BH
N Engl J Med: 15 May 2019; 380:e37 | PMID: 31091377
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Impact:
Abstract

Situs Inversus Totalis.

Gentile BA, Tighe DA


N Engl J Med: 12 Jun 2019; 380:e45
Gentile BA, Tighe DA
N Engl J Med: 12 Jun 2019; 380:e45 | PMID: 31189040
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Impact:
Abstract

Disseminated Gonococcal Infection.

Florez-Pollack S, Mauskar MM


N Engl J Med: 17 Apr 2019; 380:1565
Florez-Pollack S, Mauskar MM
N Engl J Med: 17 Apr 2019; 380:1565 | PMID: 30995376
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Impact:
Abstract

Thrombotic Thrombocytopenic Purpura.

Bhandari S, Kumar R


N Engl J Med: 17 Apr 2019; 380:e23
Bhandari S, Kumar R
N Engl J Med: 17 Apr 2019; 380:e23 | PMID: 30995377
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Impact:
Abstract

A Disturbing Decline.

Braun DA, Henderson GV, Sax PE, Miller AL, Loscalzo J


N Engl J Med: 05 Jun 2019; 380:2257-2262
Braun DA, Henderson GV, Sax PE, Miller AL, Loscalzo J
N Engl J Med: 05 Jun 2019; 380:2257-2262 | PMID: 31167056
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Impact:
Abstract

Metastatic Uveal Melanoma.

Everett L, Copperman T


N Engl J Med: 08 May 2019; 380:1853
Everett L, Copperman T
N Engl J Med: 08 May 2019; 380:1853 | PMID: 31067375
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Impact:
Abstract

Whooping Cough in a Young Infant.

Hillier D


N Engl J Med: 10 Jul 2019; 381:e4
Hillier D
N Engl J Med: 10 Jul 2019; 381:e4 | PMID: 31291519
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Impact:
Abstract

Injury from E-Cigarette Explosion.

Katz MG, Russell KW


N Engl J Med: 19 Jun 2019; 380:2460
Katz MG, Russell KW
N Engl J Med: 19 Jun 2019; 380:2460 | PMID: 31216401
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Impact:
Abstract

A STEMI Mimic.

Yu D, Blair JEA


N Engl J Med: 29 May 2019; 380:e41
Yu D, Blair JEA
N Engl J Med: 29 May 2019; 380:e41 | PMID: 31141637
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Impact:
Abstract

Case 16-2019: A 53-Year-Old Man with Cough and Eosinophilia.

Simmons RP, Dudzinski DM, Shepard JO, Hurtado RM, Coffey KC


N Engl J Med: 22 May 2019; 380:2052-2059
Simmons RP, Dudzinski DM, Shepard JO, Hurtado RM, Coffey KC
N Engl J Med: 22 May 2019; 380:2052-2059 | PMID: 31116923
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Impact:
Abstract

Infection.

Hogan CA, Schwenk H


N Engl J Med: 22 May 2019; 380:e39
Hogan CA, Schwenk H
N Engl J Med: 22 May 2019; 380:e39 | PMID: 31116922
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Impact:
Abstract

The Power and Limits of Classification - A 32-Year-Old Man with Abdominal Pain.

Stroumsa D, Roberts EFS, Kinnear H, Harris LH


N Engl J Med: 15 May 2019; 380:1885-1888
Stroumsa D, Roberts EFS, Kinnear H, Harris LH
N Engl J Med: 15 May 2019; 380:1885-1888 | PMID: 31091369
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Impact:
Abstract

Case 21-2019: A 31-Year-Old Woman with Vision Loss.

Matiello M, Juliano AF, Bowley M, Karaa A


N Engl J Med: 10 Jul 2019; 381:164-172
Matiello M, Juliano AF, Bowley M, Karaa A
N Engl J Med: 10 Jul 2019; 381:164-172 | PMID: 31291520
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Impact:
Abstract

\"Double Tongue\" Appearance in Ludwig\'s Angina.

Mohamad I, Narayanan MS


N Engl J Med: 10 Jul 2019; 381:163
Mohamad I, Narayanan MS
N Engl J Med: 10 Jul 2019; 381:163 | PMID: 31291518
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Impact:
Abstract

Weak and Winded.

Lee I, Walker JB, Nozaki K, Willett LL


N Engl J Med: 03 Jul 2019; 381:76-82
Lee I, Walker JB, Nozaki K, Willett LL
N Engl J Med: 03 Jul 2019; 381:76-82 | PMID: 31269370
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Impact:
Abstract

Pneumoperitoneum from a Gastric Perforation.

Masson A, Cheron G


N Engl J Med: 03 Jul 2019; 381:75
Masson A, Cheron G
N Engl J Med: 03 Jul 2019; 381:75 | PMID: 31269368
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Impact:
Abstract

Chronic Rhinosinusitis with Nasal Polyps.

Hopkins C


N Engl J Med: 03 Jul 2019; 381:55-63
Hopkins C
N Engl J Med: 03 Jul 2019; 381:55-63 | PMID: 31269366
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Impact:
Abstract

Nonbacterial Thrombotic Endocarditis.

Fournier JB, Testa EJ


N Engl J Med: 19 Jun 2019; 380:e48
Fournier JB, Testa EJ
N Engl J Med: 19 Jun 2019; 380:e48 | PMID: 31216402
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Impact:
Abstract

Heatstroke.

Epstein Y, Yanovich R


N Engl J Med: 19 Jun 2019; 380:2449-2459
Epstein Y, Yanovich R
N Engl J Med: 19 Jun 2019; 380:2449-2459 | PMID: 31216400
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Impact:
Abstract

Disseminated Coccidioidomycosis.

Myers RA, Zmarlicka MT


N Engl J Med: 05 Jun 2019; 380:e44
Myers RA, Zmarlicka MT
N Engl J Med: 05 Jun 2019; 380:e44 | PMID: 31167055
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Impact:
Abstract

A Disturbing Decline.

Braun DA, Simchowitz B, Henderson GV, Sax PE, Vaidya A


N Engl J Med: 29 May 2019; 380:e42
Braun DA, Simchowitz B, Henderson GV, Sax PE, Vaidya A
N Engl J Med: 29 May 2019; 380:e42 | PMID: 31141638
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Impact:
Abstract

Cutis Verticis Gyrata Associated with Acromegaly.

Parolin M, Dassie F


N Engl J Med: 01 May 2019; 380:e31
Parolin M, Dassie F
N Engl J Med: 01 May 2019; 380:e31 | PMID: 31042829
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Impact:
Abstract

Hydroxychloroquine Retinal Toxicity.

Proano C, Kimball GP


N Engl J Med: 24 Apr 2019; 380:e27
Proano C, Kimball GP
N Engl J Med: 24 Apr 2019; 380:e27 | PMID: 31018072
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Impact:
Abstract

Case 12-2019: A 60-Year-Old Man with Weakness and Difficulty Chewing.

Doughty CT, Guidon AC, Paganoni S, Hedley-Whyte ET


N Engl J Med: 17 Apr 2019; 380:1566-1574
Doughty CT, Guidon AC, Paganoni S, Hedley-Whyte ET
N Engl J Med: 17 Apr 2019; 380:1566-1574 | PMID: 30995378
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Impact:
Abstract

Diffuse Subcutaneous Emphysema.

St Clair TM, Zwemer E


N Engl J Med: 10 Apr 2019; 380:e20
St Clair TM, Zwemer E
N Engl J Med: 10 Apr 2019; 380:e20 | PMID: 30970192
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Impact:
Abstract

Cytoplasmic Blebs in T-Cell Prolymphocytic Leukemia.

Abbas HA, Han X


N Engl J Med: 12 Jun 2019; 380:2360
Abbas HA, Han X
N Engl J Med: 12 Jun 2019; 380:2360 | PMID: 31189039
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Impact:
Abstract

Case 18-2019: A 24-Year-Old Woman with a Pelvic Mass.

Spriggs DR, Melamed A, Li W, Safdar N


N Engl J Med: 12 Jun 2019; 380:2361-2369
Spriggs DR, Melamed A, Li W, Safdar N
N Engl J Med: 12 Jun 2019; 380:2361-2369 | PMID: 31189041
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Impact:
Abstract

Chronic Silicosis with Progressive Massive Fibrosis.

Riley L, Urbine D


N Engl J Med: 05 Jun 2019; 380:2256
Riley L, Urbine D
N Engl J Med: 05 Jun 2019; 380:2256 | PMID: 31167054
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Impact:
Abstract

Bull\'s-Eye Maculopathy Associated with Hydroxychloroquine.

Modi YS, Singh RP


N Engl J Med: 24 Apr 2019; 380:1656
Modi YS, Singh RP
N Engl J Med: 24 Apr 2019; 380:1656 | PMID: 31018071
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Impact:
Abstract

Traumatic Iridodialysis.

Hsiao CC, Chen WL


N Engl J Med: 10 Apr 2019; 380:1463
Hsiao CC, Chen WL
N Engl J Med: 10 Apr 2019; 380:1463 | PMID: 30970191
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Impact:
Abstract

Sepsis Guidelines.

Chen AX, Simpson SQ, Pallin DJ


N Engl J Med: 03 Apr 2019; 380:1369-1371
Chen AX, Simpson SQ, Pallin DJ
N Engl J Med: 03 Apr 2019; 380:1369-1371 | PMID: 30943343
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Impact:
Abstract

Case 20-2019: A 52-Year-Old Woman with Fever and Rash after Heart Transplantation.

Ison MG, Lebeis TA, Barros N, Lewis GD, Massoth LR


N Engl J Med: 26 Jun 2019; 380:2564-2573
Ison MG, Lebeis TA, Barros N, Lewis GD, Massoth LR
N Engl J Med: 26 Jun 2019; 380:2564-2573 | PMID: 31242366
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Impact:
Abstract

Thyroglossal Duct Cyst.

Tanitame K, Konishi H


N Engl J Med: 26 Jun 2019; 380:2563
Tanitame K, Konishi H
N Engl J Med: 26 Jun 2019; 380:2563 | PMID: 31242364
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Impact:
Abstract

Case 19-2019: A 38-Year-Old Woman with Abdominal Pain and Fever.

Khalili H, O\'Shea A, Robbins GK, Zukerberg LR


N Engl J Med: 19 Jun 2019; 380:2461-2470
Khalili H, O'Shea A, Robbins GK, Zukerberg LR
N Engl J Med: 19 Jun 2019; 380:2461-2470 | PMID: 31216403
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Impact:
Abstract

Clinical and Therapeutic Implications of Cancer Stem Cells.

Clarke MF


N Engl J Med: 05 Jun 2019; 380:2237-2245
Clarke MF
N Engl J Med: 05 Jun 2019; 380:2237-2245 | PMID: 31167052
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Impact:
Abstract

Case 17-2019: A 44-Year-Old Man with Joint Pain, Weight Loss, and Chest Pain.

Arvikar SL, Schoenfeld SR, Fox AS, Tanguturi VK, Stuart LD


N Engl J Med: 29 May 2019; 380:2157-2167
Arvikar SL, Schoenfeld SR, Fox AS, Tanguturi VK, Stuart LD
N Engl J Med: 29 May 2019; 380:2157-2167 | PMID: 31141639
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Impact:
Abstract

Coronary Arteritis in IgG4-Related Disease.

de la Fuente J, Bird J


N Engl J Med: 29 May 2019; 380:2156
de la Fuente J, Bird J
N Engl J Med: 29 May 2019; 380:2156 | PMID: 31141636
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Impact:
Abstract

Case 13-2019: A 54-Year-Old Man with Alcohol Withdrawal and Altered Mental Status.

Fenves AZ, Mojtahed A, Nisavic M, Massoth LR


N Engl J Med: 24 Apr 2019; 380:1657-1665
Fenves AZ, Mojtahed A, Nisavic M, Massoth LR
N Engl J Med: 24 Apr 2019; 380:1657-1665 | PMID: 31018073
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Impact:
Abstract

Disseminated Histoplasmosis.

Sevestre J, Hasseine L


N Engl J Med: 13 Mar 2019; 380:e13
Sevestre J, Hasseine L
N Engl J Med: 13 Mar 2019; 380:e13 | PMID: 30865801
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Impact:
Abstract

Tungiasis.

Barbosa MM, Barbosa AD


N Engl J Med: 03 Apr 2019; 380:e19
Barbosa MM, Barbosa AD
N Engl J Med: 03 Apr 2019; 380:e19 | PMID: 30943340
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Impact:
Abstract

Pneumatosis Cystoides Intestinalis with Pneumoperitoneum.

Pata F, Di Saverio S


N Engl J Med: 27 Mar 2019; 380:e17
Pata F, Di Saverio S
N Engl J Med: 27 Mar 2019; 380:e17 | PMID: 30917262
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Impact:
Abstract

Disseminated Cysticercosis.

Dev N, Abbas SZ


N Engl J Med: 27 Mar 2019; 380:1267
Dev N, Abbas SZ
N Engl J Med: 27 Mar 2019; 380:1267 | PMID: 30917261
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Impact:
Abstract

Case 8-2019: A 58-Year-Old Woman with Vision Loss, Headaches, and Oral Ulcers.

Rosenbaum JT, Rifkin LM, Buch KA, Barshak MB, Hoang MP


N Engl J Med: 13 Mar 2019; 380:1062-1071
Rosenbaum JT, Rifkin LM, Buch KA, Barshak MB, Hoang MP
N Engl J Med: 13 Mar 2019; 380:1062-1071 | PMID: 30865802
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Impact:
Abstract

Social Distance and Mobility - A 39-Year-Old Pregnant Migrant Farmworker.

Madaras L, Stonington S, Seda CH, Garcia D, Zuroweste E


N Engl J Med: 20 Mar 2019; 380:1093-1096
Madaras L, Stonington S, Seda CH, Garcia D, Zuroweste E
N Engl J Med: 20 Mar 2019; 380:1093-1096 | PMID: 30893530
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Impact:
Abstract

Heart of Gold.

Leuin S, Handwerker J


N Engl J Med: 13 Mar 2019; 380:664
Leuin S, Handwerker J
N Engl J Med: 13 Mar 2019; 380:664 | PMID: 30763189
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Impact:
Abstract

Lemierre\'s Syndrome.

Walkty A, Embil J


N Engl J Med: 20 Mar 2019; 380:e16
Walkty A, Embil J
N Engl J Med: 20 Mar 2019; 380:e16 | PMID: 30893539
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Impact:
Abstract

A Dangerous Detour.

Berg DD, Kirshenbaum J, Gay E, Vaidya A, Loscalzo J


N Engl J Med: 27 Mar 2019; 380:e18
Berg DD, Kirshenbaum J, Gay E, Vaidya A, Loscalzo J
N Engl J Med: 27 Mar 2019; 380:e18 | PMID: 30917263
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Impact:
Abstract

Case 9-2019: A 62-Year-Old Man with Atrial Fibrillation, Depression, and Worsening Anxiety.

Chen JA, Ptaszek LM, Celano CM, Beach SR


N Engl J Med: 20 Mar 2019; 380:1167-1174
Chen JA, Ptaszek LM, Celano CM, Beach SR
N Engl J Med: 20 Mar 2019; 380:1167-1174 | PMID: 30893540
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Impact:
Abstract

Case 10-2019: A 69-Year-Old Man with Progressive Dyspnea.

Black KE, Montesi SB, Feneis JF, Mark EJ


N Engl J Med: 27 Mar 2019; 380:1268-1277
Black KE, Montesi SB, Feneis JF, Mark EJ
N Engl J Med: 27 Mar 2019; 380:1268-1277 | PMID: 30917264
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Impact:
Abstract

A Dangerous Detour.

Berg DD, Kirshenbaum JM, Gay E, Miller AL, Loscalzo J


N Engl J Med: 03 Apr 2019; 380:1360-1365
Berg DD, Kirshenbaum JM, Gay E, Miller AL, Loscalzo J
N Engl J Med: 03 Apr 2019; 380:1360-1365 | PMID: 30943341
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Impact:
Abstract

Infection.

Crowe SE


N Engl J Med: 20 Mar 2019; 380:1158-1165
Crowe SE
N Engl J Med: 20 Mar 2019; 380:1158-1165 | PMID: 30893536
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Impact:
Abstract

Rhinosporidiosis.

Singh CA, Sakthivel P


N Engl J Med: 03 Apr 2019; 380:1359
Singh CA, Sakthivel P
N Engl J Med: 03 Apr 2019; 380:1359 | PMID: 30943339
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Impact:
Abstract

An Umbilical Nodule.

Barambio J, Brandariz L


N Engl J Med: 13 Mar 2019; 380:1061
Barambio J, Brandariz L
N Engl J Med: 13 Mar 2019; 380:1061 | PMID: 30865800
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Impact:
Abstract

\"Doughnut\" Lesions.

Kobayashi A, Iwasaki H


N Engl J Med: 06 Mar 2019; 380:e11
Kobayashi A, Iwasaki H
N Engl J Med: 06 Mar 2019; 380:e11 | PMID: 30855746
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Impact:
Abstract

African Tick-Bite Fever.

Mack I, Ritz N


N Engl J Med: 06 Mar 2019; 380:960
Mack I, Ritz N
N Engl J Med: 06 Mar 2019; 380:960 | PMID: 30855745
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Impact:
Abstract

Case 7-2019: A 73-Year-Old Woman with Swelling of the Right Groin and Fever.

Soumerai JD, Tajmir SH, Hirsch MS, Massoth LR


N Engl J Med: 27 Feb 2019; 380:859-868
Soumerai JD, Tajmir SH, Hirsch MS, Massoth LR
N Engl J Med: 27 Feb 2019; 380:859-868 | PMID: 30811914
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Impact:
Abstract

Spindle-Cell Sarcoma of the Tongue.

Brucoli M, Benech A


N Engl J Med: 27 Feb 2019; 380:e10
Brucoli M, Benech A
N Engl J Med: 27 Feb 2019; 380:e10 | PMID: 30811913
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Impact:
Abstract

Cardiac Metastases in Melanoma.

Safa H, Glitza Oliva IC


N Engl J Med: 27 Feb 2019; 380:858
Safa H, Glitza Oliva IC
N Engl J Med: 27 Feb 2019; 380:858 | PMID: 30811912
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Impact:
Abstract

Thrombus in Transit.

Ng J, Pelletier MP


N Engl J Med: 13 Mar 2019; 380:e8
Ng J, Pelletier MP
N Engl J Med: 13 Mar 2019; 380:e8 | PMID: 30763187
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Impact:
Abstract

Space Medicine in the Era of Civilian Spaceflight.

Stepanek J, Blue RS, Parazynski S


N Engl J Med: 13 Mar 2019; 380:1053-1060
Stepanek J, Blue RS, Parazynski S
N Engl J Med: 13 Mar 2019; 380:1053-1060 | PMID: 30865799
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Impact:
Abstract

Anatomy, Function, and Dysfunction of the Right Ventricle: JACC State-of-the-Art Review.

Sanz J, Sánchez-Quintana D, Bossone E, Bogaard HJ, Naeije R
There is increasing recognition of the crucial role of the right ventricle (RV) in determining functional status and prognosis in multiple conditions. The normal RV is anatomically and functionally different from the left ventricle, which precludes direct extrapolation of our knowledge of left-sided physiopathology to the right heart. RV adaptation is largely determined by the level of exposure to hemodynamic overload (both preload and afterload) as well as its intrinsic contractile function. These 3 processes (pressure overload, volume overload, and RV cardiomyopathy) are associated with distinct clinical course and therapeutic approach, although in reality they often coexist in various degrees. The close relationship between the RV and left ventricle (ventricular interdependence) and its coupling to the pulmonary circulation further modulate RV behavior in different clinical scenarios. In this review, the authors summarize current knowledge of RV anatomic, structural, metabolic, functional, and hemodynamic characteristics in both health and disease.

J Am Coll Cardiol: 01 May 2019; 73:1463-1482
Sanz J, Sánchez-Quintana D, Bossone E, Bogaard HJ, Naeije R
J Am Coll Cardiol: 01 May 2019; 73:1463-1482 | PMID: 30922478
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Impact:
Abstract

Tetanus.

Yen LM, Thwaites CL
Tetanus is a vaccine-preventable disease that still commonly occurs in many low-income and middle-income countries, although it is rare in high-income countries. The disease is caused by the toxin of the bacterium Clostridium tetani and is characterised by muscle spasms and autonomic nervous system dysfunction. Global vaccination initiatives have had considerable success but they continue to face many challenges. Treatment for tetanus aims to control spasms and reduce cardiovascular instability, and consists of wound debridement, antitoxin, antibiotics, and supportive care. Recent research has focused on intravenous magnesium sulphate and intrathecal antitoxin administration as methods of spasm control that can avoid the need for ventilatory support. Nevertheless, without access to mechanical ventilation, mortality from tetanus remains high. Even with such care, patients require several weeks of hospitalisation and are vulnerable to secondary problems, such as hospital-acquired infections.

Lancet: 28 Mar 2019; epub ahead of print
Yen LM, Thwaites CL
Lancet: 28 Mar 2019; epub ahead of print | PMID: 30935736
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Abstract

Multimodality imaging in ischaemic heart failure.

Bax JJ, Di Carli M, Narula J, Delgado V
In heart failure, extensive evaluation with modern non-invasive imaging modalities is needed to assess causes, pathophysiology, and haemodynamics, to determine prognosis and consider therapeutic options. This systematic evaluation includes a stepwise assessment of left ventricular size and function, the presence and severity of coronary artery disease, mitral regurgitation, pulmonary hypertension, right ventricular dilation and dysfunction, and tricuspid regurgitation. Based on this imaging-derived information, the need for specific therapies besides optimised medical therapy can be determined. The need for revascularisation, implantation of an implantable cardiac defibrillator, and mitral or tricuspid valve repair or replacement, can be (partially) guided by non-invasive imaging. Importantly, randomised controlled trials on the use of non-inasive imaging to guide therapy are scarce in this field and most non-pharmacological therapies are based on expert-consensus, but whenever trials are available, they will be addressed in this paper.

Lancet: 08 Mar 2019; 393:1056-1070
Bax JJ, Di Carli M, Narula J, Delgado V
Lancet: 08 Mar 2019; 393:1056-1070 | PMID: 30860031
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Abstract

Beyond pharmacological treatment: an insight into therapies that target specific aspects of heart failure pathophysiology.

Normand C, Kaye DM, Povsic TJ, Dickstein K
Heart failure is a common syndrome associated with substantial morbidity and mortality. The management of symptoms and the strategies for improving prognosis have largely been based on pharmacological treatments. The pathophysiology of heart failure is complex because of the multiple causes responsible for this syndrome. This Series paper presents some examples of advances in heart failure management, in which the treatment specifically targets the underlying pathophysiological mechanisms responsible for the symptoms. These treatments include treatment of electromechanical dyssynchrony and dysrhythmia by cardiac resynchronisation and implantable cardioverter-defibrillators; neurohumoral modification by baroreflex and vagal stimulation; prevention of adverse cardiac remodelling by interatrial shunts; and finally targeting the myocardium directly by cell therapy in an attempt to regenerate new myocardial cells.

Lancet: 08 Mar 2019; 393:1045-1055
Normand C, Kaye DM, Povsic TJ, Dickstein K
Lancet: 08 Mar 2019; 393:1045-1055 | PMID: 30860030
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Abstract

Iran in transition.

Danaei G, Farzadfar F, Kelishadi R, Rashidian A, ... Majdzadeh R, Malekzadeh R
Being the second-largest country in the Middle East, Iran has a long history of civilisation during which several dynasties have been overthrown and established and health-related structures have been reorganised. Iran has had the replacement of traditional practices with modern medical treatments, emergence of multiple pioneer scientists and physicians with great contributions to the advancement of science, environmental and ecological changes in addition to large-scale natural disasters, epidemics of multiple communicable diseases, and the shift towards non-communicable diseases in recent decades. Given the lessons learnt from political instabilities in the past centuries and the approaches undertaken to overcome health challenges at the time, Iran has emerged as it is today. Iran is now a country with a population exceeding 80 million, mainly inhabiting urban regions, and has an increasing burden of non-communicable diseases, including cardiovascular diseases, hypertension, diabetes, malignancies, mental disorders, substance abuse, and road injuries.

Lancet: 25 Apr 2019; epub ahead of print
Danaei G, Farzadfar F, Kelishadi R, Rashidian A, ... Majdzadeh R, Malekzadeh R
Lancet: 25 Apr 2019; epub ahead of print | PMID: 31043324
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Abstract

Heart failure drug treatment.

Rossignol P, Hernandez AF, Solomon SD, Zannad F
Heart failure is the most common cardiovascular reason for hospital admission for people older than 60 years of age. Few areas in medicine have progressed as remarkably as heart failure treatment over the past three decades. However, progress has been consistent only for chronic heart failure with reduced ejection fraction. In acutely decompensated heart failure and heart failure with preserved ejection fraction, none of the treatments tested to date have been definitively proven to improve survival. Delaying or preventing heart failure has become increasingly important in patients who are prone to heart failure. The prevention of worsening chronic heart failure and hospitalisations for acute decompensation is also of great importance. The objective of this Series paper is to provide a concise and practical summary of the available drug treatments for heart failure. We support the implementation of the international guidelines. We offer views on the basis of our personal experience in research areas that have insufficient evidence. The best possible evidence-based drug treatment (including inhibitors of the renin-angiotensin-aldosterone system and β blockers) is useful only when optimally implemented. However, implementation might be challenging. We believe that disease management programmes can be helpful in providing a multidisciplinary, holistic approach to the delivery of optimal medical care.

Lancet: 08 Mar 2019; 393:1034-1044
Rossignol P, Hernandez AF, Solomon SD, Zannad F
Lancet: 08 Mar 2019; 393:1034-1044 | PMID: 30860029
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Abstract

Leonardo da Vinci\'s studies of the brain.

Pevsner J
Leonardo da Vinci (1452-1519) contributed to the study of the nervous system. His earliest surviving anatomical drawings (circa 1485-93) included studies of the skull, brain, and cerebral ventricles. These works reflected his efforts to understand medieval psychology, including the localisation of sensory and motor functions to the brain. He was also the first to pith a frog, concluding that piercing the spinal medulla causes immediate death. After a 10-year interval in the early 1500s Leonardo resumed his anatomical studies and developed a method to inject hot wax into the ventricular system, creating a cast that showed the shape and extent of the ventricles. During this period he also progressed in his understanding of the anatomy of the cranial nerves. Besides being the first to identify the olfactory nerve as a cranial nerve, his dissections showed him that contrary to previous theories, the nerves do not converge on the lateral or third ventricles. Leonardo also performed detailed studies of the peripheral nervous system. Although his discoveries had little influence on the development of the field of anatomy, they represent an astonishingly sharp break from the field that had seen little if any progress in the previous 13 centuries. His work reflects the emergence of the modern scientific era and forms a key part of his integrative approach to art and science.

Lancet: 05 Apr 2019; 393:1465-1472
Pevsner J
Lancet: 05 Apr 2019; 393:1465-1472 | PMID: 30967217
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Abstract

Refractive surgery.

Kim TI, Del Barrio JLA, Wilkins M, Cochener B, Ang M
Refractive surgery has evolved beyond laser refractive techniques over the past decade. Laser refractive surgery procedures (such as laser in-situ keratomileusis), surface ablation techniques (such as laser epithelial keratomileusis), and photorefractive keratectomy have now been established as fairly safe procedures that produce excellent visual outcomes for patients with low-to-moderate amounts of ametropia. Additionally, a broader selection of options are now available to treat a wider range of refractive errors. Small incision lenticule extraction uses a femtosecond laser to shape a refractive lenticule, which is removed through a small wound. The potential advantages of this procedure include greater tectonic strength and less dry eye. In the future, intracorneal implants could be used to treat hyperopia or presbyopia. Phakic intraocular implants and refractive lens exchange might be useful options in carefully selected patients for correcting high degrees of ametropia. Thus, physicians are now able to provide patients with the appropriate refractive corrective option based on the individual\'s risk-benefit profile.

Lancet: 17 May 2019; 393:2085-2098
Kim TI, Del Barrio JLA, Wilkins M, Cochener B, Ang M
Lancet: 17 May 2019; 393:2085-2098 | PMID: 31106754
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Abstract

Memory editing from science fiction to clinical practice.

Phelps EA, Hofmann SG
Science fiction notions of altering problematic memories are starting to become reality as techniques emerge through which unique memories can be edited. Here we review memory-editing research with a focus on improving the treatment of psychopathology. Studies highlight two windows of memory vulnerability: initial storage, or consolidation; and re-storage after retrieval, or reconsolidation. Techniques have been identified that can modify memories at each stage, but translating these methods from animal models to humans has been challenging and implementation into clinical therapies has produced inconsistent benefits. The science of memory editing is more complicated and nuanced than fiction, but its rapid development holds promise for future applications.

Nature: 30 Jul 2019; 572:43-50
Phelps EA, Hofmann SG
Nature: 30 Jul 2019; 572:43-50 | PMID: 31367027
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Abstract

Epithelial ovarian cancer.

Lheureux S, Gourley C, Vergote I, Oza AM
Epithelial ovarian cancer generally presents at an advanced stage and is the most common cause of gynaecological cancer death. Treatment requires expert multidisciplinary care. Population-based screening has been ineffective, but new approaches for early diagnosis and prevention that leverage molecular genomics are in development. Initial therapy includes surgery and adjuvant therapy. Epithelial ovarian cancer is composed of distinct histological subtypes with unique genomic characteristics, which are improving the precision and effectiveness of therapy, allowing discovery of predictors of response such as mutations in breast cancer susceptibility genes BRCA1 and BRCA2, and homologous recombination deficiency for DNA damage response pathway inhibitors or resistance (cyclin E1). Rapidly evolving techniques to measure genomic changes in tumour and blood allow for assessment of sensitivity and emergence of resistance to therapy, and might be accurate indicators of residual disease. Recurrence is usually incurable, and patient symptom control and quality of life are key considerations at this stage. Treatments for recurrence have to be designed from a patient\'s perspective and incorporate meaningful measures of benefit. Urgent progress is needed to develop evidence and consensus-based treatment guidelines for each subgroup, and requires close international cooperation in conducting clinical trials through academic research groups such as the Gynecologic Cancer Intergroup.

Lancet: 22 Mar 2019; 393:1240-1253
Lheureux S, Gourley C, Vergote I, Oza AM
Lancet: 22 Mar 2019; 393:1240-1253 | PMID: 30910306
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Abstract

Revisiting the cold case of cold fusion.

Berlinguette CP, Chiang YM, Munday JN, Schenkel T, ... Koningstein R, Trevithick MD
The 1989 claim of \'cold fusion\' was publicly heralded as the future of clean energy generation. However, subsequent failures to reproduce the effect heightened scepticism of this claim in the academic community, and effectively led to the disqualification of the subject from further study. Motivated by the possibility that such judgement might have been premature, we embarked on a multi-institution programme to re-evaluate cold fusion to a high standard of scientific rigour. Here we describe our efforts, which have yet to yield any evidence of such an effect. Nonetheless, a by-product of our investigations has been to provide new insights into highly hydrided metals and low-energy nuclear reactions, and we contend that there remains much interesting science to be done in this underexplored parameter space.

Nature: 26 May 2019; epub ahead of print
Berlinguette CP, Chiang YM, Munday JN, Schenkel T, ... Koningstein R, Trevithick MD
Nature: 26 May 2019; epub ahead of print | PMID: 31133686
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Abstract

Reporting of Multi-Arm Parallel-Group Randomized Trials: Extension of the CONSORT 2010 Statement.

Juszczak E, Altman DG, Hopewell S, Schulz K
The quality of reporting of randomized clinical trials is suboptimal. In an era in which the need for greater research transparency is paramount, inadequate reporting hinders assessment of the reliability and validity of trial findings. The Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement was developed to improve the reporting of randomized clinical trials, but the primary focus was on parallel-group trials with 2 groups. Multi-arm trials that use a parallel-group design (comparing treatments by concurrently randomizing participants to one of the treatment groups, usually with equal probability) but have 3 or more groups are relatively common. The quality of reporting of multi-arm trials varies substantially, making judgments and interpretation difficult. While the majority of the elements of the CONSORT 2010 Statement apply equally to multi-arm trials, some elements need adaptation, and, in some cases, additional issues need to be clarified.

JAMA: 22 Apr 2019; 321:1610-1620
Juszczak E, Altman DG, Hopewell S, Schulz K
JAMA: 22 Apr 2019; 321:1610-1620 | PMID: 31012939
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Abstract

Science and health for all children with cancer.

Lam CG, Howard SC, Bouffet E, Pritchard-Jones K
Each year ~429,000 children and adolescents aged 0 to 19 years are expected to develop cancer. Five-year survival rates exceed 80% for the 45,000 children with cancer in high-income countries (HICs) but are less than 30% for the 384,000 children in lower-middle-income countries (LMICs). Improved survival rates in HICs have been achieved through multidisciplinary care and research, with treatment regimens using mostly generic medicines and optimized risk stratification. Children\'s outcomes in LMICs can be improved through global collaborative partnerships that help local leaders adapt effective treatments to local resources and clinical needs, as well as address common problems such as delayed diagnosis and treatment abandonment. Together, these approaches may bring within reach the global survival target recently set by the World Health Organization: 60% survival for all children with cancer by 2030.

Science: 14 Mar 2019; 363:1182-1186
Lam CG, Howard SC, Bouffet E, Pritchard-Jones K
Science: 14 Mar 2019; 363:1182-1186 | PMID: 30872518
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Abstract

Ushering in the next generation of precision trials for pediatric cancer.

DuBois SG, Corson LB, Stegmaier K, Janeway KA
Cancer treatment decisions are increasingly based on the genomic profile of the patient\'s tumor, a strategy called \"precision oncology.\" Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with cancer. Here, we review key factors influencing pediatric drug development in the era of precision oncology. We describe an emerging regulatory framework that is accelerating the pace of clinical trials in children as well as design challenges that are specific to trials that involve young cancer patients. Last, we discuss new drug development approaches for pediatric cancers whose growth relies on proteins that are difficult to target therapeutically, such as transcription factors.

Science: 14 Mar 2019; 363:1175-1181
DuBois SG, Corson LB, Stegmaier K, Janeway KA
Science: 14 Mar 2019; 363:1175-1181 | PMID: 30872517
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Abstract

Tuberculosis.

Furin J, Cox H, Pai M
Tuberculosis remains the leading cause of death from an infectious disease among adults worldwide, with more than 10 million people becoming newly sick from tuberculosis each year. Advances in diagnosis, including the use of rapid molecular testing and whole-genome sequencing in both sputum and non-sputum samples, could change this situation. Although little has changed in the treatment of drug-susceptible tuberculosis, data on increased efficacy with new and repurposed drugs have led WHO to recommend all-oral therapy for drug-resistant tuberculosis for the first time ever in 2018. Studies have shown that shorter latent tuberculosis prevention regimens containing rifampicin or rifapentine are as effective as longer, isoniazid-based regimens, and there is a promising vaccine candidate to prevent the progression of infection to the disease. But new tools alone are not sufficient. Advances must be made in providing high-quality, people-centred care for tuberculosis. Renewed political will, coupled with improved access to quality care, could relegate the morbidity, mortality, and stigma long associated with tuberculosis, to the past.

Lancet: 19 Mar 2019; epub ahead of print
Furin J, Cox H, Pai M
Lancet: 19 Mar 2019; epub ahead of print | PMID: 30904262
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Abstract

Outcomes of transcatheter aortic valve replacement without predilation of the aortic valve: Insights from 1544 patients included in the SOURCE 3 registry.

Dumonteil N, Terkelsen C, Frerker C, Collart F, ... Lefèvre T,
Aims
To investigate the impact of transcatheter aortic valve replacement (TAVR) without preliminary balloon aortic valvuloplasty (pre-BAV) on periprocedural outcomes in a large, real-world registry.
Methods and results
The SOURCE 3 registry was an observational, multi-center, single-arm study of patients with severe, symptomatic aortic stenosis at high surgical risk treated with the SAPIEN 3 transcatheter heart valve (THV). Procedural and 30-day outcomes were compared between two groups of 772 patients each (retrospectively matched) with or without pre-BAV. All baseline clinical, echocardiographic, and anatomical valve characteristics were comparable between groups except for Society of Thoracic Surgeons (STS) score, which was lower in the direct TAVR group (6.0 ± 5.9 vs 7.8 ± 8.3; p = 0.003). In the direct TAVR group, there were less post-dilatations (8.1% vs. 13.1%, p = 0.002), shorter procedural time (70.9 ± 39.8 min vs 73.0 ± 32.2 min, p = 0.033) and fluoroscopy time (13.4 ± 7.0 min vs 14.9 ± 7.4 min, p < 0.001). Other procedural outcomes and echocardiographic variables at 30 days did not differ significantly between the two groups: safety endpoint (10.4% with pre-BAV vs 13.5% with direct TAVR, p = 0.059), mortality (2.1% vs 2.3%, p = 0.730), disabling strokes (0.4% vs 0.5%, p = 0.704), and moderate to severe paravalvular leak (PVL) (3.2% vs 2.2%, p = 0.40). Unexpectedly, new permanent pacemaker implantation and life-threatening bleeds were less frequently observed with pre-BAV group than with direct TAVR (10.4% vs 13.9%, p = 0.032 and 3.5% vs 6.5%, p = 0.007, respectively).
Conclusion
In this large TAVR dataset, direct implantation of the SAPIEN 3 THV without pre-BAV was feasible and safe and resulted in shorter procedures, without impact on 30-day prosthesis function and PVL.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Int J Cardiol: 30 Nov 2019; 296:32-37
Dumonteil N, Terkelsen C, Frerker C, Collart F, ... Lefèvre T,
Int J Cardiol: 30 Nov 2019; 296:32-37 | PMID: 31256993
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Abstract

The challenge of antimicrobial resistance: What economics can contribute.

Roope LSJ, Smith RD, Pouwels KB, Buchanan J, ... Robotham JV, Wordsworth S
As antibiotic consumption grows, bacteria are becoming increasingly resistant to treatment. Antibiotic resistance undermines much of modern health care, which relies on access to effective antibiotics to prevent and treat infections associated with routine medical procedures. The resulting challenges have much in common with those posed by climate change, which economists have responded to with research that has informed and shaped public policy. Drawing on economic concepts such as externalities and the principal-agent relationship, we suggest how economics can help to solve the challenges arising from increasing resistance to antibiotics. We discuss solutions to the key economic issues, from incentivizing the development of effective new antibiotics to improving antibiotic stewardship through financial mechanisms and regulation.

Science: 04 Apr 2019; 364
Roope LSJ, Smith RD, Pouwels KB, Buchanan J, ... Robotham JV, Wordsworth S
Science: 04 Apr 2019; 364 | PMID: 30948524
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Abstract

Communication with children and adolescents about the diagnosis of a life-threatening condition in their parent.

Dalton L, Rapa E, Ziebland S, Rochat T, ... Stein A,
Many adults diagnosed with a life-threatening condition have children living at home; they and their partners face the dual challenge of coping with the diagnosis while trying to maintain a parenting role. Parents are often uncertain about how, when, and what to tell their children about the condition, and are fearful of the effect on their family. There is evidence that children are often aware that something is seriously wrong and want honest information. Health-care professionals have a key role in supporting and guiding parents and caregivers to communicate with their children about the diagnosis. However, the practical and emotional challenges of communicating with families are compounded by a scarcity of evidence-based guidelines. This Review considers children\'s awareness and understanding of their parents\' condition, the effect of communication around parental life-threatening condition on their wellbeing, factors that influence communication, and the challenges to achieving effective communication. Children\'s and parents\' preferences about communication are outlined. An expert workshop was convened to generate principles for health-care professionals, intended as practical guidance in the current absence of empirically derived guidelines.

Lancet: 15 Mar 2019; 393:1164-1176
Dalton L, Rapa E, Ziebland S, Rochat T, ... Stein A,
Lancet: 15 Mar 2019; 393:1164-1176 | PMID: 30894272
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Abstract

cGAS in action: Expanding roles in immunity and inflammation.

Ablasser A, Chen ZJ
DNA is highly immunogenic. It represents a key pathogen-associated molecular pattern (PAMP) during infection. Host DNA can, however, also act as a danger-associated molecular pattern (DAMP) and elicit strong inflammatory responses. The cGAS-STING pathway has emerged as a major pathway that detects intracellular DNA. Here, we highlight recent advances on how cGAS and STING mediate inflammatory responses and how these are regulated, allowing cells to readily respond to infections and noxious agents while avoiding the inappropriate sensing of self-DNA. A particular focus is placed on the role of cGAS in the context of sterile inflammatory conditions. Manipulating cGAS or STING may open the door for new therapeutic strategies for the treatment of acute and chronic inflammation relevant to many human diseases.

Science: 07 Mar 2019; 363
Ablasser A, Chen ZJ
Science: 07 Mar 2019; 363 | PMID: 30846571
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