A novel hepcidin mutation.

BACKGROUND: The bioactive peptide hormone hepcidin-25 regulates iron levels by inhibiting iron transport to plasma via ferroportin. Hepcidin-25 is synthesized in the liver where the 84 amino acids pro-hepcidin is cleaved into the bioactive hepcidin-25. A patient admitted to the hospital presented with infertility and fatigue. METHODS: Genomic DNA was purified from whole blood using the Maxwell 16 system (Promega). MLPA analysis was performed to detect large genomic rearrangements using the SALSA MLPA kit # P347, Hemochromatosis (MRC Holland, Holland). Plasma hepcidin measurements were performed using liquid chromatography/tandem mass spectrometry (LC-MS/MS). RESULTS: A novel HAMP mutation (homozygous one base deletion in c.215delG, p.Cys72Serfs*?) was detected. The deletion in nucleotide 215 causes a frameshift altering the predicted protein sequence from cysteine13 in mature peptide. Whether this leads to nonsense mediated decay of the mRNA or synthesis of an aberrant peptide in unknown, but bioactive hepcidin-25 was undetectable in plasma. The patient had massive iron overload with ferritin up to 8360 µg/L. He was anaemic with a Hb at 7.0 mmol/L (11.3 g/dL) and suffered from hypogonadotropic hypogonadism with a total testosterone of 1.2 nmol/l. Continued treatment with venesection and gonadotropins led to reduced fatigue, reduction in iron overload, a normalized Hb and improvement of semen quality. CONCLUSION: A novel hepcidin mutation was detected in a patient with massive iron overload, fatigue and hypogonadotropic hypogonadism.

National clinical practice guidelines for the treatment of symptomatic gallstone disease: 2021 recommendations from the Danish Surgical Society.

BACKGROUND AND OBJECTIVE: Gallstones are highly prevalent, and more than 9000 cholecystectomies are performed annually in Denmark. The aim of this guideline was to improve the clinical course of patients with gallstone disease including a subgroup of high-risk patients. Outcomes included reduction of complications, readmissions, and need for additional interventions in patients with uncomplicated gallstone disease, acute cholecystitis, and common bile duct stones (CBDS). METHODS: An interdisciplinary group of clinicians developed the guideline according to the GRADE methodology. Randomized controlled trials (RCTs) were primarily included. Non-RCTs were included if RCTs could not answer the clinical questions. Recommendations were strong or weak depending on effect estimates, quality of evidence, and patient preferences. RESULTS: For patients with acute cholecystitis, acute laparoscopic cholecystectomy is recommended (16 RCTs, strong recommendation). Gallbladder drainage may be used as an interval procedure before a delayed laparoscopic cholecystectomy in patients with temporary contraindications to surgery and severe acute cholecystitis (1 RCT and 1 non-RCT, weak recommendation). High-risk patients are suggested to undergo acute laparoscopic cholecystectomy instead of drainage (1 RCT and 1 non-RCT, weak recommendation). For patients with CBDS, a one-step procedure with simultaneous laparoscopic cholecystectomy and CBDS removal by laparoscopy or endoscopy is recommended (22 RCTs, strong recommendation). In high-risk patients with CBDS, laparoscopic cholecystectomy is suggested to be included in the treatment (6 RCTs, weak recommendation). For diagnosis of CBDS, the use of magnetic resonance imaging or endoscopic ultrasound prior to surgical treatment is recommended (8 RCTs, strong recommendation). For patients with uncomplicated symptomatic gallstone disease, observation is suggested as an alternative to laparoscopic cholecystectomy (2 RCTs, weak recommendation). CONCLUSIONS: Seven recommendations, four weak and three strong, for treating patients with symptomatic gallstone disease were developed. Studies for treatment of high-risk patients are few and more are needed. ENDORSEMENT: The Danish Surgical Society.

Hereditary hemochromatosis: data from a single center Copenhagen cohort.

OBJECTIVES: We aimed to describe a cohort of hereditary hemochromatosis (HH) patients from a single urban center in Copenhagen. METHODS: Retrospectively, data from patients with HH from the years 2009-2020 were collected. RESULTS: A total of 203 patients was recorded. Males constituted 65.0% of the patients. Homozygous HH (HHH)/compound heterozygous HH (CHH) accounted for 69.4%/30.6%. HHH patients had significantly higher ferritin and transferrin saturation (TS) levels at debut than CHH patients. Fifty-five HHH patients (39.0%) had ferritin >1000 ug/L versus 9 (14.5%) in the CHH group (p < .001). Age at debut did not differ between female and male patients. Ferritin (but not TS) levels were significantly higher in male patients. The proportion of patients with ferritin >1000 did not differ between males and females. One-hundred patients (49.3%) had one or more symptoms at the time of diagnosis; arthralgias of the metacarpophalangeal joints and/or ankles (n = 46 (22.7%)), fatigue (n = 67 (33.0%)) and decreased libido (n = 20 (9.9%)). The proportion of patients with symptoms did not differ between HHH and CHH or between male and female patients. Severe organ complications (cardiomyopathy, late onset type 1 diabetes or cirrhosis) were present in 14 patients (6.9%). CONCLUSIONS: We report a high proportion of compound HH, constituting almost one-third of patients. We found that the proportion of patients with symptoms did not differ between HHH and CHH and recommend that CHH should be treated and examined in the same way as HHH.

Sexual dysfunction after inguinal hernia repair with the Onstep versus Lichtenstein technique: A randomized clinical trial.

BACKGROUND: Sequelae after inguinal hernia repair include pain-related impairment of sexual function. Pain during intercourse can originate from the scar, scrotum, penis, or during ejaculation. The aim of this study was to investigate if the Onstep technique resulted in better results than the Lichtenstein technique regarding pain-related impairment of sexual function. METHODS: This study was part of the randomized ONLI trial (NCT01753219, Onstep versus Lichtenstein for inguinal hernia repair). Separate reporting of pain-related impairment of sexual function was planned before the study start, with a separate sample size calculation. Participants were randomized to the Onstep or Lichtenstein technique for repair of their primary inguinal hernia and followed up at 6 months postoperative with the use of a questionnaire specific for pain-related impairment of sexual function. RESULTS: A total of 259 patients completed the 6-month follow-up, 129 in the Lichtenstein group and 130 in the Onstep group. Among the patients operated with the Onstep technique, 17 experienced pain during sexual activity 6 months after operation compared with 30 patients operated with the Lichtenstein technique (P = .034). Both subgroups that experienced pain during sexual activity had a median visual analog scale score of 0 with an interquartile range of 0 to 2 (P = .349). The Lichtenstein technique resulted in new pain in 14 patients, whereas the Onstep procedure gave new pain in 7 patients (P = .073). CONCLUSION: The Onstep technique was superior to the Lichtenstein technique in terms of pain during sexual activity 6 months after operation.

Chronic pain after inguinal hernia repair with the ONSTEP versus the Lichtenstein technique, results of a double-blinded multicenter randomized clinical trial.

PURPOSE: The open new simplified totally extraperitoneal (ONSTEP) technique for the repair of inguinal hernia was presented some years ago with promising initial results regarding chronic pain. We conducted a randomized clinical trial investigating the ONSTEP technique versus the Lichtenstein technique with focus on postoperative pain. The aim of this paper was to report the results regarding chronic pain from follow-up at 6 and 12 months for the participants in the ONSTEP versus Lichtenstein trial. METHODS: This study was conducted as a randomized double-blinded clinical trial in male participants with primary unilateral hernias, having surgical repair of their hernia at one of five participating general surgical departments. At surgery, participants were allocated (1:1) to the ONSTEP or the Lichtenstein technique for inguinal hernia repair. Participants were followed up with questionnaires at 6 and 12 months. The primary outcome was the proportion of patients with substantial pain-related impairment of daily functions at 6- and 12-month follow-ups. RESULTS: From April 2013 to May 2014, 290 male patients were included in the study. Regarding follow-up for pain, a total of 259 patients (89%) completed the 6-month follow-up and a total of 236 patients (81%) completed the 12-month follow-up. Regarding pain at the 6- and 12-month follow-ups, no difference was found between groups. Two patients operated with Lichtenstein technique developed severe disabling chronic pain postoperatively, which was not seen in the ONSTEP group. CONCLUSION: The ONSTEP technique was not superior to the Lichtenstein technique regarding chronic pain following repair of primary inguinal hernias in males. TRIAL REGISTRATION: https://clinicaltrials.gov NCT01753219.

Striking presence of Egyptian blue identified in a painting by Giovanni Battista Benvenuto from 1524.

Egyptian blue has been identified in a painting from 1524 by the Italian artist Ortolano Ferrarese (Giovanni Battista Benvenuto). Egyptian blue is the oldest known synthetic pigment, invented by the Egyptians in the fourth dynasty (2613-2494 BC) of the Old Kingdom and extensively used throughout Antiquity. From about 1000 A.D., it disappeared from the historical record and was only reinvented in the late nineteenth and early twentieth century. The discovery of Egyptian blue in Ortolano Ferrarese's painting from 1524 shows that Egyptian blue was in fact available in the period from which it is normally considered not to exist. The identification of Egyptian blue is based on optical microscopy supported by energy-dispersive spectroscopy and visual light photon-induced spectroscopy, and finally confirmed by Raman microspectroscopy.