COVID-19 in solid organ transplant recipients: A national cohort study from Sweden

Solid organ transplant (SOT) recipients run a high risk for adverse outcomes from COVID-19, with reported mortality around 19%. We retrospectively reviewed all known Swedish SOT recipients with RT-PCR confirmed COVID-19 between March 1 and November 20, 2020 and analyzed patient characteristics, management, and outcome. We identified 230 patients with a median age of 54.0 years (13.2), who were predominantly male (64%). Most patients were hospitalized (64%), but 36% remained outpatients. Age >50 and male sex were among predictors of transition from outpatient to inpatient status. National early warning Score 2 (NEWS2) at presentation was higher in non-survivors. Thirty-day all-cause mortality was 9.6% (15.0% for inpatients), increased with age and BMI, and was higher in men. Renal function decreased during COVID-19 but recovered in most patients. SARS-CoV-2 antibodies were identified in 78% of patients at 1–2 months post-infection. Nucleocapsid-specific antibodies decreased to 38% after 6–7 months, while spike-specific antibody responses were more durable. Seroprevalence in 559 asymptomatic patients was 1.4%. Many patients can be managed on an outpatient basis aided by risk stratification with age, sex, and NEWS2 score. Factors associated with adverse outcomes include older age, male sex, greater BMI, and a higher NEWS2 score.     

History of cyclodialysis. In memory of Leopold Heine 1870-1940

Cyclodialysis, introduced 1905 by Leopold Heine and vehemently debated at first, has later been recognized all over the world, mainly for treating open angle glaucoma and glaucoma in aphacic eyes. Various modifications of the primary surgical technique have been recommended, among them the combination of cyclodialysis with other antiglaucomatous interventions as well as the implantation of tissue-components or foreign material into the cyclodialysis cleft. Apparently, successful cyclodialysis results in both an increased aqueous outflow into the suprachorioidal space and in a reduced aqueous production. Nowadays, cyclodialysis seems to be outdated almost completely by laser-trabeculoplasty and by trabecelectomy. However, cyclodialysis may still be helpful in otherwise uncontrollable glaucomas or may regain a new importance, if microsurgically performed "ab interno."     

血清CD44及其拼接变异体sCD44v6测定对肺癌的诊治意义

目的：探讨测定血清中可溶性ＣＤ４４含量在肺癌中的临床意义。方法：用酶联免疫吸附试验（ＥＬＩＳＡ）检测４５例肺癌患者及１８例正常人血清中可溶性ＣＤ４４ｓ（ｓＣＤ４４ｓ）和可溶性ＣＤ４４ｖ６（ｓＣＤ４４ｖ６）的含量,结果：化疗前肺鳞癌和腺癌患者血清ｓＣＤ４４ｓ和ｓＣＤ４４ｖ６水平明显高于小细胞肺癌（ＳＣＬＣ）患者和正常组,差异非常显著;ＳＣＬＣ与正常人比较差异无显著性;非小细胞肺癌（ＮＳＣＬＣ）Ⅲ＋Ⅳ     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

Effects of LSD and BOL on the catecholamine synthesis and turnover in various brain regions

In the rat, lysergic acid diethylamide (LSD) 0.5 mg/kg and 2-bromo lysergic acid diethylamide (BOL) 0.5 mg/kg increased the rate of the striatal in vivo tyrosine hydroxylation as measured by the DOPA accumulation after decarboxylase inhibition. Neither LSD nor BOL significantly changed the DOPA accumulation in the olfactory tubercle, a dopamine-rich part of the limbic system. LSD but not BOL increased the DOPA accumulation in the cerebral cortex and in the brain stem. LSD and BOL appeared not to alter the rate of -MT-induced disappearance of DA or of NA in the whole brain, nor did they change the rate of the -MT-induced disappearance of DA in the striatum. It is suggested that in the striatum LSD and BOL block autoreceptors (presynaptic receptors) regulating the tyrosine hydroxylation. These receptors may be DA receptors, but may also be 5-HT- or LSD-sensitive receptors.The regional differences observed between LSD and BOL suggest that LSD in the cerebral cortex and in the brain stem increases the DOPA accumulation by mechanism other than that functioning in the striatum. One possible explanation is that LSD and BOL may differ in their effects on 5-hydroxytryptaminergic systems in the cerebral cortex and in the brain stem.     

Prognostic potential of flow cytometric S-phase and ploidy prospectively determined in primary breast carcinomas

In a prospective study of a consecutive breast cancer series accumulated in the period 1978–82, the S-phase fraction (SPF) and ploidy status were determined by flow cytometry performed on cell nuclei derived from samples of 580 primary tumors. Sixty percent of the tumors were non-diploid. After correction for debris the median SPF values were 7.3% overall, 12% for non-diploid tumors, and 2.9% for diploid tumors (2.6% when nodal subsets N2 and N3 and cases with metastases at presentation were excluded). The SPF values correlated both to tumor size (p=0.008) and to the number of positive axillary lymph nodes (p=0.03).At clinical follow-up in 1986, 467 unilateral breast cancer patients who had undergone radical treatment for cure could be evaluated with respect to the prognostic value of both the SPF value and ploidy status. The median duration of follow-up was then 59 months (range 2–90), and the median time-to-recurrence 24 months (range 2–69, n=137).At follow-up in 1991, 201/467 of the patients had died, the median duration of follow-up being 50 months (range 2–126) for the deceased, and 119 (range 6–148) for the survivors. In multivariate analysis (Cox's proportional hazards models), the strongest independent predictors of distant recurrence-free survival (DRFS) were the number of positive axillary lymph nodes (p<0.0001), the debris-corrected SPF value alone (p=0.003,versus p=0.05 for uncorrected value), and ploidy status combined with the corrected SPF value (p=0.0002). When age was taken into account, both the corrected SPF value and the ploidy-SPF combination were predictors of crude survival (p=0.006 and p=0.002, respectively).In univariate life-table analysis, the 5-year DRFS rate was 93% in node-negative (N0) cases with an SPF<7.3%, as compared to 80% in those with an SPF7.3% (p=0.005). Among node-positive cases, the prognostic value of the SPF was confined to those with 1–3 positive nodes, the 5-year DRFS rate being 68% in cases with an SPF<7.3%, as compared to 40% in cases with an SPF7.3% (p=0.01).Ploidy status and SPF were combined to form four groups: diploid & SPF<2.6% (DL), diploid & SPF2.6% (DH), non-diploid & SPF<12% (NDL), and non-diploid & SPF12% (NDH). Among node-negative patients, the DRFS rate fell from 95% in the DL group to 87% in the NDL group, with the DH group at an intermediate level, as compared with 74% (p=0.03) for the NDH group which accounted for the bulk of the early distant recurrences. Among patients with 1–3 positive lymph nodes, the 5-year DRFS rate was 68% in both the groups with low SPF values (DL and NDL), as compared with 45% in the DH group (p=0.03), and 37% in the NDH group (p=0.006).In this study, the flow cytometry SPF value, alone or in combination with ploidy status, yielded the most profound additional prognostic information, enabling both node-negative patients with a high probability of cure and patients at risk of early relapse to be identified. Among node-positive patients, the prognostic value of the SPF value was confined to those with 1–3 positive axillary lymph nodes (the predominant node-positive subgroup), enabling a high and a low DRFS rate subgroup to be distinguished – a useful distinction where selection for adjuvant drug treatment is concerned. As the predictive strength of the SPF value was enhanced when correction was made for debris, we would recommend that the effect of such factors as debris be minimized as far as possible when flow cytometry-derived SPF values are to be used for prognostic purposes.     

Clinical classification of Swedish snuff dippers'' lesions supported by histology

From a total material of 184 Swedish users of loose packed moist snuff and 68 users of portion-bag packed moist snuff, cases were selected from subgroups based on a four-point clinical grading scale. The selected material for the study comprised 70 cases (ten from each clinical grade group, no Degree 4 lesion was found among portion-bag users). Features recognized in biopsies from these cases together with findings in previous studies correlated well with the use of a four-point scale for the grading of clinical changes, especially in the context of discriminating lesions for which special efforts should be undertaken to make the patient stop or change the snuff dipping habit and for selecting patients in whom regular clinical follow-up including a biopsy should be carried out. In this article is also discussed the labeling of the clinical oral mucosal changes seen at the site where a quid of snuff is regularly placed. The conceptual use of "snuff dippers' lesions" is recommended instead of e.g. snuff-induced leukoplakia.     

Pancreatic tumors in multiple endocrine neoplasia type 1: Clinical presentation and surgical treatment

Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-erm outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors. This strategy should be applied especially in patients with aggressive family histories to possibly reduce the risk of malignant tumor progression.

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Resumen Entre 33 individuos con tumores pancréaticos endocrinos como componente del síndrome de neoplasia endocrina múltiple tipo 1 (NEM-1), 19 pacientes (58%) tenían hipergastrinemia, 7 (21%) hiperinsulinismo y 7 (21%) lesiones clínicas no funcionantes. En la totalidad de los pacientes sometidos a cirugía pancreática fue hallado por lo menos un tumor, incluso en aquellos con examenes de localización negativos anteriores a la operación. Estos pacientes también albergaban tumores macroscópicos, así como numerosos microadenomas; con frecuencia las lesiones demostraron inmunocoloración con diferentes hormonas, principalmente polipéptido, insulina, glucagón y somatostatina. Se encontraron lesiones endocrinas duodenales en 4 de cada 5 pacientes investigados, las cuales colorearon con gastrina y anticuerpos a la somatostatina. Se practicó resección pancreática distal (principalmente resección subtotal) en 18 pacientes, eventualmente combinada con enucleación del tumor (cuando éste se hallaba ubicado en la cabeza del páncreas) o duodenectomía; solamente unos pocos pacientes fueron sometidos a simple enucleación del tumor o al procedimiento de Whipple. El resultado a largo plazo fue más favorable en los pacientes con hiperinsulinismo, puesto que sólo uno presentó recurrencia clínica. Los pacientes con hipergastrinemia exhibieron apenas una disminución transitoria de los valores de gastrina sérica luego de la cirugía pancreática. Cuarenta y siete por ciento del conjunto tuvo o desarrolló metástasis, en tanto que la extensión local del tumor se presentó en 57% de los casos con lesiones no funcionantes. Nueve pacientes murieron por progresión de la neoplasia en el curso del seguimiento. En acuerdo con sugerencias previas, se considero quo la cirugía está indicada en pacientes con NEM-1 e hiperinsulinismo, aún en los casos en que no se visualiza radiológicamente la lesión, pero que la indicación puede ser ampliada para incluir también pacientes con sólo marcadores bioquímicos, tales como niveles elevados de gastrina, indicativos de la presencia de tumores macroscópicos. Esta estrategia debe ser aplicada principalmente en aquellos pacientes con historia familiar agresiva, con lo cual tal vez se reduce el riesgo de progesión maligna del tumor.

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Résumé Parmi 33 patients ayant une tumeur pancréatique endocrine due à une néoplasie endocrine multiple de type 1 (MEN-1), 19 (58%) avaient une hypergastrinémie, 7 (21%) un hyperinsulinisme et 7 (21%) une lésion cliniquement muette. On a mis en évidence au minimum une grosse tumeur chez tous les patients, y compris chez ceux dont les examens préopératoires de dépistage tumoral étaient négatifs. Les patients étaient également porteurs de tumeurs macroscopiques et de nombreux microadénomes. Les lésions montraient souvent un immunomarquage positif pour de multiples hormones, principalement le polypeptide pancréatique, l'insuline, le glucagon et la somatostatine. Des lésions endocrines duodénales furent retrouvées chez 4 des 5 patients explorés; elles montraient un immunomarquage avec les anticorps angigastrine et anti-somatostatine. Une résection pancréatique distale, le plus souvent subtotale, a été réalisée chez 18 patients. Elle était éventuellement complétée par une énucléation tmorale de la tête ou par une duodénotomie. Peu de patients ont bénéficié d'une simple énucléation ou d'une intervention de Whipple. L'évolution postopératoire à long terme a été plus favorable en cas d'insulinome puisque seul un patient a eu une récidive clinique. Les patients atteints de gastrinome n'ont présenté que transitoirement une diminution des taux sériques de gastrine après la chirurgie pancréatique. Quarante sept pour cent de ces patients avaient ou ont développé des métastases contre 57% des patients porteurs de lésions sans traduction clinique. Neuf patients sont décédés en raison de l'extension tumorale au cours du suivi. Conformément à des suggestions antérieures, la chirurgie semble indiquée chez les patients atteints de MEN-1 avec hyperinsulinisme même si la radiologie ne visualise pas de lésion. Mais cette indication peut être élargie aux patients dont seuls les paramètres biologiques sont en faveur d'une grosse tumeur (dont l'hypergastrinémie). Cette stratégie pourrait convenir particulièrement aux patients ayant des antécédents familiaux importants; elle permettrait peut-être de réduire le risque d'extension tumorale.

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Presented at the International Association of Endocrine Surgeons in Stockholm, Sweden, August, 1991.     

Method for Dissection of Mesenteric Metastases in Mid-gut Carcinoid Tumors

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.     

谷胱甘肽对顺铂致猴和大鼠肾细胞毒性的影响

目的 探讨顺铂对猴和大鼠肾小管上皮细胞的毒性及半胱氨酸和GSH合成抑制剂BSO对其影响。方法 从猴和大鼠的肾脏分离培养的肾小管上皮细胞接种于96孔培养板，培养24h后加入一系列浓度的顺铂，或在加入顺铂前16和4h，分别加入GSH合成抑制剂BSO和GSH的前体物半胱氨酸，继续培养，分别在8、24和48h3个时间点用MTT方法检测细胞存活率。结果 顺铂对猴和大鼠肾小管上皮细胞有明显的毒性，在不同的时间点有各自的剂量—反应关系，顺铂对大鼠肾小管上皮细胞在8、24和48h 3个时间点半数抑制浓度(IC50)分别为1105．12、513．25和71．24μmol/L；BSO能使3组IC50均降低，分别为66．00、21．43和7．23μmol/L，而半胱氨酸则使3组IC50均升高，均大于5000μmol/L；顺铂对猴肾小管上皮细胞在3个时间点IC50分别为3026．00、1238．35和664．44μmol/L；BS0使3组ICD分别降为480．10、108．61和31．43μmol/L，而半胱氨酸则可使3组IC50均大于5000μmol/L。结论 顺铂对猴和大鼠肾小管上皮细胞均具有明显毒性作用，对猴的毒性低于大鼠；BS0可增强顺铂的细胞毒性，对大鼠的影响大于猴，而半胱氨酸对两种细胞的保护作用无显著性差异，提示细胞内GSH对顺铂所致肾小管上皮细胞毒性有保护作用。