The presence of serum anti-SARS-CoV-2 IgA appears to protect primary health care workers from COVID-19.

The patterns of humoral and cellular responses to SARS-CoV-2 were studied in Swedish primary health care workers (n = 156) for 6 months during the Covid-19 pandemic. Serum IgA and IgG to SARS-CoV-2, T-cell proliferation and cytokine secretion, demographic and clinical data, PCR-verified infection, and self-reported symptoms were monitored. The multivariate method OPLS-DA was used to identify immune response patterns coupled to protection from Covid-19. Contracting Covid-19 was associated with SARS-CoV-2-specific neutralizing serum IgG, T cell, IFN-γ, and granzyme B responses to SARS-CoV-2, self-reported typical Covid-19 symptoms, male sex, higher BMI, and hypertension. Not contracting Covid-19 was associated with female sex, IgA-dominated, or no antibody responses to SARS-CoV-2, airborne allergy, and smoking. The IgG-responders had SARS-CoV-2-specific T-cell responses including a cytotoxic CD4+ T-cell population expressing CD25, CD38, CD69, CD194, CD279, CTLA-4, and granzyme B. IgA-responders with no IgG response to SARS-CoV-2 constituted 10% of the study population. The IgA responses were partially neutralizing and only seen in individuals who did not succumb to Covid-19. To conclude, serum IgG-dominated responses correlated with T-cell responses to SARS-CoV-2 and PCR-confirmed Covid-19, whereas IgA-dominated responses correlated with not contracting the infection.

Radiographic and Symptomatic Knee Osteoarthritis 32 to 37 Years After Acute Anterior Cruciate Ligament Rupture.

BACKGROUND: The long-term prevalence of knee osteoarthritis (OA) after anterior cruciate ligament (ACL) injury is unknown, especially in patients without a history of ACL surgery. PURPOSE: To (1) describe the prevalence of radiographic OA, symptomatic OA, and knee replacement surgery 32 to 37 years after acute ACL injury and to (2) compare the prevalence of radiographic OA, symptomatic OA, and knee symptoms between patients allocated to early ACL surgery or no ACL surgery and patients who crossed over to ACL surgery. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Participants aged 15 to 40 years at the time of ACL injury were allocated to surgical (augmented or nonaugmented ACL repair) or nonsurgical ACL treatment within 14 days of injury. At 32 to 37 years after the initial injury, 153 participants were followed up with plain weightbearing radiographs and completed 4 subscales from the Knee injury and Osteoarthritis Outcome Score (KOOS). Radiographic OA was defined as Kellgren and Lawrence grade 2 or higher. Symptomatic OA was defined as radiographic OA plus knee symptoms measured with the KOOS. RESULTS: Participants allocated to ACL surgery (n = 64) underwent surgery at a mean ± SD of 5 ± 4 days (range, 0-11 days) after injury. Of the 89 participants allocated to no ACL surgery, 53 remained nonsurgically treated, 27 had ACL surgery within 2 years, and 9 had ACL surgery between 3 and 21 years after injury. In the total sample, 95 participants (62%) had radiographic tibiofemoral OA, including 11 (7%) who had knee replacement. The prevalence of radiographic tibiofemoral OA was lower in the group allocated to ACL surgery compared with the group who never had ACL surgery (50% vs 75%; P = .005). The prevalence of symptomatic OA (50% in the total sample) and patellofemoral radiographic OA (35% in the total sample) was similar between groups. CONCLUSION: Patients allocated to early ACL surgery, performed a mean 5 days after injury, had a lower prevalence of tibiofemoral radiographic OA at 32 to 37 years after injury compared with patients who never had ACL surgery. The prevalences of symptomatic OA, radiographic patellofemoral OA, and knee symptoms were similar irrespective of ACL treatment. Overall, the prevalence of OA after ACL injury was high. REGISTRATION: NCT03182647 (ClinicalTrials.gov identifier).

[Mortality among hospitalized patients did not appear to increase during the summer]. / Mortalitet bland sjukhusvårdade tycktes inte öka under sommaren - Analys från Universitetssjukhuset i Linköping.

A retrospective review of medical records (2017-2018) at Linköping University Hospital compared hospital mortality for the 2-month period of summer vacations (group A) with two months of regular activity (group B). The mortality was 163 patients in group A and 216 in group B. Emergency admittance dominated (95%) in both groups. Comorbidity was found in 81%, and at admittance the risk for death during the hospital stay was estimated to more than 50% in three out of four patients. There was no difference between the groups regarding demography, hospital stay, or diagnosis. Due to a 30% reduction of hospital beds during the summer some patients were relocated to other specialties. No relocated patient died in group A but six in group B. Eight deaths were judged as probably preventable, but none definitely preventable. The similarity between the groups regarding mortality does not allow estimations of differences in adverse events in general. Low mortality among relocated patients is probably due to identification of high-risk patients not suitable for relocation.

Women with acute intermittent porphyria have a defect in 5α-steroid production during the menstrual cycle.

OBJECTIVE: To measure serum concentrations of progesterone, estradiol and 5α- and 5ß-reduced progesterone metabolites in the follicular and luteal phases of the menstrual cycle in women with latent acute intermittent porphyria and manifest acute intermittent porphyria in comparison with healthy control women. DESIGN: A descriptive study with repeated measurements during a complete, ovulatory menstrual cycle. SETTING: University hospital out-patient clinic. POPULATION: Thirty-two women with DNA-diagnosed acute intermittent porphyria and 20 healthy control women. METHODS: Blood samples for serum progesterone, estradiol, allopregnanolone and pregnanolone were drawn on predefined menstrual cycle days, twice in the follicular phase and three times in the luteal phase. Serum levels of estradiol and progesterone were analysed with commercial kits. Allopregnanolone and pregnanolone levels were analysed with radioimmunoassay following diethylether extraction and celite column chromatography. MAIN OUTCOME MEASURES: Changes in serum levels of progesterone, estradiol, allopregnanolone and pregnanolone throughout the menstrual cycle. RESULTS: Women with acute intermittent porphyria displayed lower serum concentrations of allopregnanolone in comparison with healthy control women, the difference being most prominent in the luteal phase (p < 0.001). Levels of pregnanolone did not differ significantly between groups. No significant difference was found between women with latent acute intermittent porphyria and manifest acute intermittent porphyria. CONCLUSIONS: Decreased levels of the 5α-reduced progesterone metabolite allopregnanolone were found in the menstrual cycle of women with acute intermittent porphyria. This has not been reported previously and could indicate a reduced 5α-reductase type 1 capacity in the ovary and liver among these women.

Evaluation of gonadotropin-releasing hormone agonist treatment for prevention of menstrual-related attacks in acute porphyria.

OBJECTIVE: To describe the benefits and adverse effects of gonadotropin-releasing hormone (GnRH) agonist treatment for prevention of recurrent menstrual attacks in women with acute intermittent porphyria and variegate porphyria. To describe concomitant add-back therapies with estradiol and progesterone and describe their benefits and adverse effects. DESIGN: A retrospective follow-up with questionnaires, interviews and medical records. SETTING: Out-patient care at the Umeå University Hospital in Sweden. POPULATION: Sixteen Caucasian women with DNA-diagnosed porphyria and menstrual-cycle-related porphyria attacks were treated with GnRH agonists during 1984-2000. Fourteen women participated. The mean age when treatment started was 33 years (17-48 years). The duration of treatment varied between 5 months and 9 years. METHODS: GnRH agonists were administered by the intranasal route or by injections. To reduce menopausal symptoms, add-back therapy with low doses of estradiol was administered, and for endometrial protection progesterone was usually administered. MAIN OUTCOME MEASURES: Treatment effects and adverse events as detected in questionnaires, interviews and medical records. RESULTS: Eleven women reported benefits from GnRH agonist treatment with less intense and/or less frequent porphyria attacks, and in four of them attacks almost disappeared. Two women reported no change. One woman had only temporary improvement. Porphyria attacks were triggered by solely estradiol add-back in two women and in five of nine women when progesterone was given. CONCLUSIONS: GnRH agonist treatment can ameliorate menstrual-cycle-related attacks of porphyria. Dose findings for GnRH agonists and add-back regimes especially for progesterone are intricate.

Clinical aspects of acute intermittent porphyria in northern Sweden: a population-based study.

The objective of this study was to update the clinical issues of acute intermittent porphyria (AIP), as they have not been in focus for years, and to be aware of potentially associated disorders and social consequences. A total of 356 gene carriers of AIP from northern Sweden participated in this retrospective population-based study. Eight mutations were found with a predominance of W198X (89%). Clinical manifestations of AIP (manifest AIP) were identified in 42%, 65% were women. Women were more severely stricken by AIP attacks concerning number and duration, hospital admission and early onset. Men reporting most attacks were > 40 years of age. In addition to traditional symptoms during attacks, fatigue was commonly described. Chronic AIP symptoms and disability pension due to AIP were reported in about 20% of subjects. Precipitating factors were reported with evident sex differences. Half of the gene carriers who were on medications used drugs considered not safe (in 1999), mainly antihypertensive drugs. Smoking was associated with high AIP attack frequency. Elevated levels of ALT, bile acids, creatinine, U-ALA and U-PBG and decreased levels of creatinine clearance were associated with manifest AIP. The same was true for hypertension and myalgia in the legs. Hepatoma was strikingly overrepresented. The high prevalence of manifest AIP in this study could be explained by a mutation-dependent penetrance. Our results emphasize the importance of early diagnosis, counselling and treatment of attacks, screening and treatment of associated disorders.