Guideline-discordant care among females undergoing groin hernia repair: the importance of sex as a biologic variable.

PURPOSE: Females suffer higher rates of operative recurrence and chronic pain following groin hernia repair. Guidelines recommend minimally invasive (MIS) groin hernia repair as the preferred approach to reduce these adverse outcomes. It is unknown what proportion of females receive MIS hernia repair. Therefore, our goal was to investigate adoption of evidence-based practices in groin hernia repair using sex as a biological variable. METHODS: Retrospective cohort study of adults undergoing elective groin hernia repair (2014-2019) within a statewide quality improvement collaborative. Primary outcome was surgical approach. Multivariable logistic regression was performed to analyze the likelihood of undergoing MIS hernia repair. Secondary outcomes were 30-day adjusted rates of clinical and patient-reported outcomes (PROs). PROs included regret to undergo surgery among patients who completed post-operative surveys. RESULTS: Among 23,723 patients, the majority (90.7%) were males. Compared to males, females less often underwent an MIS surgical approach (37.4% vs 45.1%, p < 0.0001). After adjustment for patient and clinical variables, females remained significantly less likely to undergo MIS groin hernia repair (aOR 0.88, 95% CI 0.80-0.97). Adjusted clinical outcomes were not different between males and females. Among 4325 patients who completed post-operative surveys, adjusted rates of regret to undergo surgery were higher among females (12.9% vs 8.5%, p = 0.003). CONCLUSIONS: Even after adjusting for differences, females were less likely to receive guideline-concordant groin hernia repair and were more likely to regret surgery. Understanding the behaviors of surgeons who treat females with groin hernia may inform quality metrics to promote best practices in this population.

2S protein Ara h 7.0201 has unique epitopes compared to other Ara h 7 isoforms and is comparable to 2S proteins Ara h 2 and 6 in basophil degranulation capacity.

BACKGROUND: Screening for specific IgE against 2S albumin proteins Ara h 2 and 6 has good positive predictive value in diagnosing peanut allergy. From the third 2S member Ara h 7, 3 isoforms have been identified. Their allergenicity has not been elucidated. OBJECTIVE: This study investigated the allergenicity of Ara h 7 isoforms compared to Ara h 2 and 6. METHODS: Sensitization of 15 DBPCFC-confirmed peanut-allergic patients to recombinant Ara h 2.0201, Ara h 6.01 and isoforms of recombinant Ara h 7 was determined by IgE immunoblotting strips. A basophil activation test (BAT) was performed in 9 patients to determine IgE-cross-linking capacities of the allergens. Sensitivity to the allergens was tested in 5 patients who were sensitized to at least 1 Ara h 7 isoform, by a concentration range in the BAT. 3D prediction models and sequence alignments were used to visualize differences between isoforms and to predict allergenic epitope regions. RESULTS: Sensitization to Ara h 7.0201 was most frequent (80%) and showed to be equally potent as Ara h 2.0201 and 6.01 in inducing basophil degranulation. Sensitization to Ara h 7.0201 together with Ara h 2.0201 and/or 6.01 was observed, indicating the presence of unique epitopes compared to the other 2 isoforms. Differences between the 3 Ara h 7 isoforms were observed in C-terminal cysteine residues, pepsin and trypsin cleavage sites and 3 single amino acid substitutions. CONCLUSION & CLINICAL RELEVANCE: The majority of peanut-allergic patients are sensitized to isoform Ara h 7.0201, which is functionally as active as Ara h 2.0201 and 6.01. Unique epitopes are most likely located in the C-terminus or an allergenic loop region which is a known allergenic epitope region for Ara h 2.0201 and 6.01. Due to its unique epitopes and allergenicity, it is an interesting candidate to improve the diagnostic accuracy for peanut allergy.

Dose dependent molecular effects of acrylamide and glycidamide in human cancer cell lines and human primary hepatocytes.

Recently published studies suggest a weak positive correlation between increased dietary acrylamide intake and the increased risk of endometrial and ovarian cancer. However, risk assessment of acrylamide remains difficult because the carcinogenic mechanisms are still unknown and in particular the molecular effects of low level acrylamide exposure as seen by dietary intake are not well understood. Therefore, we analyzed in ovarian and endometrial cancer cell lines as well as in primary hepatocytes the expression of genes involved in cancer development and xenobiotic metabolism after high and low dose exposure (1-0.001mM) of acrylamide and its metabolite glycidamide. In conclusion our in vitro results demonstrate that exposure to high doses of glycidamide/acrylamide - exceeding the dietary exposure of the general population by far - can induce genes with growth promoting potential like the oncogene cMYC and genes involved in the MAPK pathway. However, low-dose exposure seems to activate primarily genes involved in the elimination of the toxicant.

[Reimbursement of new medical therapy]. / Erstattungsfähigkeit neuartiger Arzneimitteltherapien.

Medical progress poses a new financial challenge for the German statutory health insurance. In order to assure the stability of the German statutory health insurance all services have to be economical, but on the other hand the health care system allows access to new therapy in the ambulant and in-patient sector. This article describes in detail how new therapies are reimbursed.

Outreach and screening following the 2005 London bombings: usage and outcomes.

BACKGROUND: Little is known about how to remedy the unmet mental health needs associated with major terrorist attacks, or what outcomes are achievable with evidence-based treatment. This article reports the usage, diagnoses and outcomes associated with the 2-year Trauma Response Programme (TRP) for those affected by the 2005 London bombings.MethodFollowing a systematic and coordinated programme of outreach, the contact details of 910 people were obtained by the TRP. Of these, 596 completed a screening instrument that included the Trauma Screening Questionnaire (TSQ) and items assessing other negative responses. Those scoring ≥6 on the TSQ, or endorsing other negative responses, received a detailed clinical assessment. Individuals judged to need treatment (n=217) received trauma-focused cognitive-behaviour therapy (TF-CBT) or eye movement desensitization and reprocessing (EMDR). Symptom levels were assessed pre- and post-treatment with validated self-report measures of post-traumatic stress disorder (PTSD) and depression, and 66 were followed up at 1 year. RESULTS: Case finding relied primarily on outreach rather than standard referral pathways such as primary care. The effect sizes achieved for treatment of DSM-IV PTSD exceeded those usually found in randomized controlled trials (RCTs) and gains were well maintained an average of 1 year later. CONCLUSIONS: Outreach with screening, linked to the provision of evidence-based treatment, seems to be a viable method of identifying and meeting mental health needs following a terrorist attack. Given the failure of normal care pathways, it is a potentially important approach that merits further evaluation.

Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype.

A unique feature of the tumor cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA methylation, are involved in this silencing of many B-cell-associated genes. Here, we show that DNA demethylation alone or in conjunction with histone acetylation is not able to reconstitute the B-cell-gene expression program in cultured HRS cells. Instead, combined DNA demethylation and histone acetylation of B-cell lines induce an almost complete extinction of their B-cell-expression program and a tremendous upregulation of numerous Hodgkin-characteristic genes, including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the upregulation of Hodgkin-characteristic genes and the extinction of the B-cell-expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic upregulation of Hodgkin-characteristic genes thus plays--in addition to promoter DNA hypermethylation of B-cell-associated genes--a pivotal role for the reprogramming of HRS cells and explains why DNA demethylation alone is unable to reconstitute the B-cell-expression program in HRS cells.

Clinical two-photon microendoscopy.

Two-photon medical imaging has found its way into dermatology as an excellent method for noninvasive skin cancer detection without need of contrast agents as well as for in situ drug screening of topically-applied cosmetical and pharmaceutical components. There is an increasing demand to apply the multiphoton technology also for deep-tissue skin imaging as well as for intracorporal imaging. We report on the first clinical use of multiphoton endoscopes, in particular of a miniaturized rigid two-photon GRIN lens endoscope. The microendoscope was attached to the multiphoton tomograph DermaInspect and employed to detect the extracellular matrix proteins collagen and elastin in the human dermis of volunteers and patients with ulcera by in vivo second harmonic generation and in vivo two-photon autofluorescence.

[Current patient education problems for the physician]. / Aktuelle Aufklärungsprobleme für den Arzt.

Every medical treatment which involves risk to the patient requires the informed consent of the patient. Taking into account the fundamental right of the patient to remain physically unscathed and the right of self-determination, proper information must be given to the patient regarding typical risks. This is a prerequisite to patient consent. In this regard, the law makes strong demands. Even in cases where medical treatment is unsuccessful due to complications beyond the physician's control, the physician is still held liable (even if there was no fault found in his medical treatment) if he had not properly informed his patient of the risk involved in the procedure or he cannot prove that he had informed the patient. The following paper explains the legal demands of the duty to inform patients along with examples of precedents.