Necrotizing Pancreatitis from Hypertriglyceridemia: More Severe Disease?

BACKGROUND: Necrotizing pancreatitis (NP) is caused by hypertriglyceridemia (HTG) in up to 10% of patients. Clinical experience suggests that HTG-NP is associated with increased clinical severity; objective evidence is limited and has not been specifically studied in NP. AIM: The aim of this study was to critically evaluate outcomes in HTG-NP. We hypothesized that patients with HTG-NP had significantly increased severity, morbidity, and mortality compared to patients with NP from other etiologies. METHODS: A case-control study of all NP patients treated at a single institution between 2005 and 2018 was performed. Diagnostic criteria of HTG-NP included a serum triglyceride level > 1000 mg/dL and the absence of another specific pancreatitis etiology. To control for differences in age, sex, and comorbidities, non-HTG and HTG patients were matched at a 4:1 ratio using propensity scores. Outcomes were compared between non-HTG and HTG patients. RESULTS: A total of 676 NP patients were treated during the study period. The incidence of HTG-NP was 5.8% (n = 39). The mean peak triglyceride level at diagnosis was 2923 mg/dL (SEM, 417 mg/dL). After propensity matching, no differences were found between non-HTG and HTG patients in CT severity index, degree of glandular necrosis, organ failure, infected necrosis, necrosis intervention, index admission LOS, readmission, total hospital LOS, or disease duration (P = NS). Mortality was similar in non-HTG-NP (7.1%) and HTG-NP (7.7%), P = 1.0. CONCLUSION: In this large, single-institution series, necrotizing pancreatitis caused by hypertriglyceridemia had similar disease severity, morbidity, and mortality as necrotizing pancreatitis caused by other etiologies.

Clinical criteria for integrated molecular pathology in intraductal papillary mucinous neoplasm: less is more.

BACKGROUND: For pancreatic cysts with negative cytology, Integrated Molecular Pathology (IMP) is a malignancy risk score integrating clinical criteria with pancreatic cyst fluid DNA profiling. Aside from main pancreatic duct (MPD) diameter, integrated clinical criteria are not International Consensus Guidelines High-Risk Stigmata. We predicted exclusion of clinical criteria except MPD diameter could simplify the IMP and better distinguish invasive/malignant disease. METHODS: Records of >1100 patients with IPMN were reviewed retrospectively. Sensitivity, specificity, and accuracy of conventional IMP for invasive/malignant disease was compared to DNA profile including only MPD ≥10mm (IMP-10.) Invasive outcomes were invasive-IPMN/adenocarcinoma on surgical pathology, pathologic or radiographic evidence of invasive/metastatic disease during surveillance. Malignant outcomes included high grade dysplastic IPMN (HGD-IPMN). RESULTS: 225 patients who met study criteria underwent 283 IMP evaluations: 98 followed by surgery, 185 followed by ≥ 23 months surveillance. IMP-10 had greater specificity (90.1% vs. 73.7%) and accuracy (89.8% vs. 74.2%) for invasive disease compared to IMP in surgery + surveillance patients, but lower sensitivity (77.8% vs. 88.9%). Trends were similar in surgery patients alone and malignant outcome analyses. CONCLUSION: IMP-10 excludes less-reliable clinical factors resulting in greater accuracy in predicting invasive/malignant disease and fewer patients with benign disease being recommended for surgery.

Quantitative detection of human spermatogonia for optimization of spermatogonial stem cell culture.

STUDY QUESTION: Can human spermatogonia be detected in long-term primary testicular cell cultures using validated, germ cell-specific markers of spermatogonia? SUMMARY ANSWER: Germ cell-specific markers of spermatogonia/spermatogonial stem cells (SSCs) are detected in early (1-2 weeks) but not late (> 6 weeks) primary testicular cell cultures; somatic cell markers are detected in late primary testicular cell cultures. WHAT IS KNOWN ALREADY: The development of conditions for human SSC culture is critically dependent on the ability to define cell types unequivocally and to quantify spermatogonia/SSCs. Growth by somatic cells presents a major challenge in the establishment of SSC cultures and therefore markers that define spermatogonia/SSCs, but are not also expressed by testicular somatic cells, are essential for accurate characterization of SSC cultures. STUDY DESIGN, SIZE, DURATION: Testicular tissue from eight organ donors with normal spermatogenesis was used for assay validation and establishing primary testicular cell cultures. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunofluorescence analysis of normal human testicular tissue was used to validate antibodies (UTF1, SALL4, DAZL and VIM) and then the antibodies were used to demonstrate that primary testicular cells cultured in vitro for 1-2 weeks were composed of somatic cells and rare germ cells. Primary testicular cell cultures were further characterized by comparing to testicular somatic cell cultures using quantitative reverse transcriptase PCR (UTF1, FGFR3, ZBTB16, GPR125, DAZL, GATA4 and VIM) and flow cytometry (CD9 and SSEA4). MAIN RESULTS AND THE ROLE OF CHANCE: UTF1, FGFR3, DAZL and ZBTB16 qRT-PCR and SSEA4 flow cytometry were validated for the sensitive, quantitative and specific detection of germ cells. In contrast, GPR125 mRNA and CD9 were found to be not specific to germ cells because they were also expressed in testicular somatic cell cultures. While the germ cell-specific markers were detected in early primary testicular cell cultures (1-2 weeks), their expression steadily declined over time in vitro. After 6 weeks in culture only somatic cells were detected. LIMITATIONS, REASONS FOR CAUTION: Different groups attempting SSC culture have utilized different sources of human testes and minor differences in the preparation and maintenance of the testicular cell cultures. Differences in outcome may be explained by genetic background of the source tissue or technical differences. WIDER IMPLICATIONS OF THE FINDINGS: The ability to propagate human SSCs in vitro is a prerequisite for proposed autologous transplantation therapy aimed at restoring fertility to men who have been treated for childhood cancer. By applying the assays validated here it will be possible to quantitatively compare human SSC culture conditions. The eventual development of conditions for long-term propagation of human SSCs in vitro will greatly facilitate learning about the basic biology of these cells and in turn the ability to use human SSCs in therapy. STUDY FUNDING/COMPETING INTERESTS: The experiments presented in this manuscript were funded by a Project Development Team within the ICTSI NIH/NCRR Grant Number TR000006. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

What is the impact of hypogammaglobulinemia on the rate of infections and survival in solid organ transplantation? A meta-analysis.

Hypogammaglobulinemia has been described after solid organ transplantation and has been associated with increased risk of infections. The aim of the study was to evaluate the rate of severe hypogammaglobulinemia and its relationship with the risk of infections during the first year posttransplantation. Eighteen studies (1756 patients) that evaluated hypogammaglobulinemia and posttransplant infections were included. The data were pooled using the DerSimonian and Laird random-effects model. Q statistic method was used to assess statistical heterogeneity. Within the first year posttransplantation, the rate of hypogammaglobulinemia (IgG < 700 mg/dL) was 45% (95% CI: 0.34-0.55; Q = 330.1, p < 0.0001), the rate of mild hypogammaglobulinemia (IgG = 400-700 mg/dL) was 39% (95% CI: 0.22-0.56; Q = 210.09, p < 0.0001) and the rate of severe hypogammaglobulinemia (IgG < 400 mg/dL) was 15% (95% CI: 0.08-0.22; Q = 50.15, p < 0.0001). The rate of hypogammaglobulinemia by allograft type: heart 49% (21%-78%; Q = 131.16, p < 0.0001); kidney 40% (30%-49%; Q = 24.55, p = 0.0002); liver 16% (0.001%-35%; Q = 14.31, p = 0.0002) and lung 63% (53%-74%; Q = 6.85, p = 0.08). The odds of respiratory infection (OR = 4.83; 95% CI: 1.66-14.05; p = 0.004; I(2) = 0%), CMV (OR = 2.40; 95% CI: 1.16-4.96; p = 0.02; I(2) = 26.66%), Aspergillus (OR = 8.19; 95% CI: 2.38-28.21; p = 0.0009; I(2) = 17.02%) and other fungal infections (OR = 3.69; 95% CI: 1.11-12.33; p = 0.03; I(2) = 0%) for patients with IgG < 400 mg/dL were higher than the odds for patients with IgG > 400 mg/dL. The odds for 1-year all-cause mortality for severe hypogammaglobulinemia group was 21.91 times higher than those for IgG > 400 mg/dL group (95% CI: 2.49-192.55; p = 0.005; I(2) = 0%). Severe hypogammaglobulinemia during the first year posttransplantation significantly increased the risk of CMV, fungal and respiratory infections, and was associated with higher 1-year all-cause mortality.

[Nonorganic (functional) hearing loss in children]. / Nichtorganische (funktionelle) Hörstörungen bei Kindern.

Nonorganic (functional) hearing loss in children is characterized by hearing loss without a detectable corresponding pathology in the auditory system. It is not an uncommon disease in childhood. Typically, there is a discrepancy between elevated pure tone thresholds and normal speech discrimination in everyday life. We evaluated 85 original publications, 27 reviews and 4 textbook articles. Mean age at diagnosis was 11.3 years. Girls were affected twice as often as boys. Patient histories showed a high prevalence of emotional and school problems. Pre-existing organic hearing loss can be worsened by nonorganic causes. A brainstem audiometry should confirm the diagnosis. The differential diagnosis includes auditory processing disorder, elevated thresholds in mental retardation and auditory neuropathy. We recommend taking a personal history including biographical factors, a psychological assessment including intelligence testing and referral to a child psychiatrist. Prognosis seems to be dependent on the severity of the patient's school and/or personal problems. Categorization following the Austen-Lynch model can be a valuable prognostic factor.

Opioid analgesia in necrotizing pancreatitis: Incidence and timing of a hidden crisis.

BACKGROUND: Rates of opioid usage during necrotizing pancreatitis (NP) disease course are unknown. We hypothesized that a significant number of NP patients were prescribed opioid analgesics chronically. METHODS: Single institution IRB-approved retrospective study of 230 NP patients treated between 2015 and 2019. RESULTS: Data were available for 198/230 (86%) patients. 166/198 (84%) were discharged from their index hospitalization with a prescription for an opioid. At the first clinic visit following hospitalization, 110/182 (60%) were using opioids. Six months after disease onset, 72/163 (44%) continued to require opioids. At disease resolution, 38/144 (26%) patients remained on opioid medications. The rate of active opioid prescriptions at six months after disease onset declined throughout the period studied from 68% in 2015 to 39% in 2019. CONCLUSIONS: Opioid prescriptions are common in NP. Despite decline over time, 1 in 4 patients remain on opioids at disease resolution. These data identify an opportunity to adjust analgesic prescription practice in NP patients.

[Identifying language and communication disorders as part of the medical curriculum]. / Erkennen von Sprach- und Sprechstörungen als Lerninhalt des Medizinstudiums.

BACKGROUND: Like hearing loss, language and speech disorders can also lead to impaired communication. Speech and language disorders can occur at any age, for example as a specific language impairment, stuttering, dysarthria, and aphasia. Hence, irrespective of their speciality, there is a high probability that physicians will at some point encounter communication-impaired patients, be required to classify their disorder and refer them for appropriate therapy. METHODS: A new module entitled 'communication disorders' consisting of two teaching units was integrated in the practical course 'ENT--phoniatrics--pedaudiology' for undergraduate clinical students in 2008. The learning objective of the first unit was to identify and classify communication disorders, presented using sound and video data, by means of simple criteria. The module was evaluated on the basis of questionnaires completed by 164 students. RESULTS: On a scale of 1-7, the evaluation showed overall positive results with 6.54 (highest score) for professional competence and 5.32 (lowest score) for discussion. The overall score was 12.28 out of a possible maximum of 15 points. CONCLUSION: The ability to identify communication impairments is an important medical skill. Since communication disorders are common diseases we suggest that this skill be incorporated in the medical curriculum. Thus we have introduced a module for communication disorders; its evaluation by students shows a high level of satisfaction in each category. After developing specific diagnostic indicators students were able to independently describe and identify communication disorders.

[Pedaudiological diagnostics in the first year of life . Clinical follow-up, risk factors, and middle ear function]. / Pädaudiologische Diagnostik im ersten Lebensjahr. Klinische Verläufe, Risikofaktoren und Mittelohrfunktion.

The universal neonatal hearing screening (UNHS) program demands detection of hearing loss within the first 3 months of life. Practicability and different screening methods should be evaluated. Thus, 617 patients (329 m., 288 w.) were analyzed; 246 children were referred in the UNHS, 389 with risk factors. In 459 children (74%), automated auditory brainstem response (ABR) screening in our department excluded hearing loss, thereof 129 (21%) underwent diagnostic auditory brainstem-evoked audiometry responses: 20 (16%) showed normal and 109 (84%) elevated ABR thresholds. A total of 91 children (83%) received hearing aids and 11 children (10%) treatment of middle ear effusion. Hearing loss was diagnosed in 18% of all children, 24% with UNHS referral and 34% with both referral and risk factors. Craniofacial anomalies, premature birth < 32 weeks of pregnancy, and syndromes were the most frequent risk factors. Reevaluation by ABR showed an improvement to normal hearing in 3 (of 14) children. The 226 Hz compared to 1,000 Hz-tympanometry showed different specificity (95.5 vs. 85.5%) and sensitivity (32.5 vs. 57.1%). Diagnosis within 3 months is possible, but very challenging in children with risk factors.

Diffusion-weighted imaging in characterization of cystic pancreatic lesions.

AIM: To evaluate whether apparent diffusion coefficient (ADC) measurements from diffusion-weighted imaging (DWI) can characterize or predict the malignant potential of cystic pancreatic lesions. MATERIALS AND METHODS: Retrospective review of the magnetic resonance imaging (MRI) database over a 2-year period revealed 136 patients with cystic pancreatic lesions. Patients with DWI studies and histological confirmation of cystic mass were included. In patients with known pancreatitis, lesions with amylase content of >1000 IU/l that resolved on subsequent scans were included as pseudocysts. ADC of cystic lesions was measured by two independent reviewers. These values were then compared to categorize these lesions as benign or malignant using conventional MRI sequences. RESULTS: Seventy lesions were analysed: adenocarcinoma (n=4), intraductal papillary mucinous neoplasm (IPMN; n=28), mucinous cystic neoplasm (MCN; n=9), serous cystadenoma (n=16), and pseudocysts (n=13). There was no difference between ADC values of malignant and non-malignant lesions (p=0.06), between mucinous and serous tumours (p=0.12), or between IPMN and MCN (p=0.42). ADC values for low-grade IPMN were significantly higher than those for high-grade or invasive IPMN (p=0.03). CONCLUSION: ADC values may be helpful in deciding the malignant potential of IPMN. However, they are not useful in differentiating malignant from benign lesions or for characterizing cystic pancreatic lesions.

Routine Gastric Decompression after Pancreatoduodenectomy: Treating the Surgeon?

BACKGROUND: The decision to routinely leave a nasogastric tube after pancreatoduodenectomy remains controversial. We sought to determine the impact of immediate nasogastric tube removal versus early nasogastric tube removal (<24 h) on postoperative outcomes. METHODS: A retrospective review of our institution's prospective ACS-NSQIP database identified patients that underwent pancreatoduodenectomy from 2015 to 2018. Outcomes were compared among patients with immediate nasogastric tube removal versus early nasogastric tube removal. RESULTS: A total of 365 patients were included in primary analysis (no nasogastric tube, n = 99; nasogastric tube removed <24 h, n = 266). Thirty-day mortality and infectious, renal, cardiovascular, and pulmonary morbidity were similar in comparing those with no nasogastric tube versus early nasogastric tube removal on univariable and multivariable analyses (P > 0.05). Incidence of delayed gastric emptying (11.1 versus 13.2%) was similar between groups. Patients with no nasogastric tube less frequently required nasogastric tube reinsertion (n = 4, 4%) compared to patients with NGT <24 h (n = 39, 15%) (OR = 3.83, 95% CI [1.39-10.58]; P = 0.009). CONCLUSION: Routine gastric decompression can be safely avoided after uneventful pancreaticoduodenectomy.

[Do children with cochlear implants read or write differently?: literacy acquisition after cochlear implantation]. / Lesen und schreiben CI-Kinder anders?: Schriftspracherwerb nach Versorgung mit einem Cochlear implant.

BACKGROUND: Despite the fact that literacy acquisition in hearing impaired children is frequently hampered, reading and writing competences continue not to be regularly evaluated and documented in children fitted with cochlear implants (CI). In this 2-year longitudinal study literacy acquisition in children fitted with CI was investigated. PATIENTS AND METHODS: In total, 18 pre- and primary school children fitted with CI who had suffered prelingual deafness were examined. Subjects' ages at CI fitting ranged from 0.9 to 5.9 years; they were raised orally and monolingual German and showed normal intellectual achievement. Familial risk of developing dyslexia was ruled out. To assess subjects' literacy acquisition precursor and partial abilities in reading and writing according to dual route and developmental models were examined three times within 2 years. Precursor abilities included development of vocabulary and phonological awareness. Partial abilities were mastery in sublexical and lexical word processing in reading and writing as well as auditory and visual working memory. RESULTS: Subjects showed a broad range in performance regarding vocabulary development as well as literacy. Discrepant results in terms of age equivalent visual and underachievement in auditory working memory as well as good achievement in implicit phonological awareness and weakness in explicit demands on phoneme analysis and manipulation of phonemes can be described. Indications were that subjects tended towards lip reading the instructor's item presentation. Performance in the administered writing test reveals a preference for lexical word processing, whereas sublexical word processing seems to make relatively higher demands on subjects. CONCLUSIONS: Easier processing of visual information in partial and precursor abilities are consistent with a tendency to prefer a visual-lexical processing strategy. The presented study stresses the importance of generally assessing reading and writing skills when evaluating language development in children supplied with cochlear implants. Partial and precursor abilities should be included in order to identify any delay in development promptly. Thus, individual qualitative characteristics can be addressed in therapeutic intervention.

Comparison of skin closure techniques in patients undergoing open pancreaticoduodenectomy: A single center experience.

BACKGROUND: This study evaluated closure techniques and incisional surgical site complications (SSCs) and incisional surgical site infections (SSIs) after pancreaticoduodenectomy (PD). METHODS: Retrospective review of open PDs from 2015 to 2018 was performed. Outcomes were compared among closure techniques (subcuticular + topical skin adhesive (TSA); staples; subcuticular only). SSCs were defined as abscess, cellulitis, seroma, or fat necrosis. SSIs were defined according to the National Surgical Quality Improvement Program (NSQIP). RESULTS: Patients with subcuticular + TSA (n = 205) were less likely to develop an incisional SSC (9.8%) compared to staples (n = 139) (20.1%) and subcuticular (n = 74) (16.2%) on univariable analysis (P = 0.024). Multivariable analysis revealed no statistically significant difference in incisional SSC between subcuticular + TSA and subcuticular (P = 0.528); a significant difference remained between subcuticular + TSA and staples (P = 0.014). Unadjusted median length of stay (LOS) (days) was significantly longer for staples (9) vs. subcuticular (8) vs. subcuticular + TSA (7); P < 0.001. Incisional SSIs were evaluated separately according to the NSQIP definition. When comparing rates, the subcuticular + TSA group experienced lower incisional SSIs compared to the other two techniques (4.9% vs. 10.1%, 10.8%). However, this difference was not statistically significant by either univariable or multivariable analysis. CONCLUSIONS: Subcuticular suture + TSA reduces the risk of incisional SSCs when compared to staples alone after pancreaticoduodenectomy.

Hepatic Steatosis After Neoadjuvant Chemotherapy for Pancreatic Cancer: Incidence and Implications for Outcomes After Pancreatoduodenectomy.

BACKGROUND: This study aimed to determine the incidence of new onset hepatic steatosis after neoadjuvant chemotherapy for pancreatic cancer and its impact on outcomes after pancreatoduodenectomy. METHODS: Retrospective review identified patients who received neoadjuvant chemotherapy for pancreatic adenocarcinoma and underwent pancreatoduodenectomy from 2013 to 2018. Preoperative computed tomography scans were evaluated for the development of hepatic steatosis after neoadjuvant chemotherapy. Hypoattenuation included liver attenuation greater than or equal to 10 Hounsfield units less than tissue density of spleen on noncontrast computed tomography and greater than or equal to 20 Hounsfield units less on contrast-enhanced computed tomography. RESULTS: One hundred forty-nine patients received neoadjuvant chemotherapy for a median of 5 cycles (interquartile range (IQR), 4-6). FOLFIRINOX was the regimen in 78% of patients. Hepatic steatosis developed in 36 (24%) patients. The median time from neoadjuvant chemotherapy completion to pancreatoduodenectomy was 40 days (IQR, 29-51). Preoperative biliary stenting was performed in 126 (86%) patients. Neoadjuvant radiotherapy was delivered to 23 (15%) patients. Female gender, obesity, and prolonged exposure to chemotherapy were identified as risk factors for chemotherapy-associated hepatic steatosis. Compared with control patients without neoadjuvant chemotherapy-associated hepatic steatosis, patients developing steatosis had similar rates of postoperative pancreatic fistula (8% (control) vs. 4%, p = 0.3), delayed gastric emptying (8% vs. 14%, p = 0.4), and major morbidity (11% vs. 15%, p = 0.6). Ninety-day mortality was similar between groups (8% vs. 2%, p = 0.08). CONCLUSION: Hepatic steatosis developed in 24% of patients who received neoadjuvant chemotherapy but was not associated with increased morbidity or mortality after pancreatoduodenectomy.

[A new gene locus for an autosomal-dominant non-syndromic hearing impairment (DFNA 33) is situated on chromosome 13q34-qter]. / Ein neuer Genort für eine autosomal-dominante, nichtsyndromale Schwerhörigkeit (DFNA33) liegt auf Chromosom 13q34-qter.

By investigation of a German family pedigree with non-syndromic hearing impairment of early onset and autosomal-dominant mode of inheritance, linkage to known DFNA loci was excluded, and the existence of a new locus (DFNA33) was revealed. In a subsequent genomic scan the phenotype was mapped to a 6 cM interval on chromosome 13q34-qter. A maximum two-point lod score of 2.96 was obtained for the marker D13S285 with a maximum lod score in the multipoint analysis of 3.28 at 124.56 cM.

[A new locus for an autosomal dominant, non-syndromic hearing impairment (DFNA57) located on chromosome 19p13.2 and overlapping with DFNB15]. / Ein neuer Genort für eine autosomal dominante, nichtsyndromale Hörstörung (DFNA57) kartiert auf Chromosom 19p13.2 und überlappt mit DFNB15.

BACKGROUND: Non-syndromic hearing loss is the most genetically heterogeneous trait known in humans. To date, 54 loci for autosomal dominant non-syndromic sensorineural hearing loss (NSSHL) have been identified by linkage analysis. METHODS: In this study a German pedigree has been identified segregating a progressive bilateral loss of lower and middle frequencies. RESULTS: A genome-wide screening and linkage analysis revealed the existence of a new NSSHL locus (DFNA57). The phenotype was mapped to a 10 degrees Mbp interval on chromosome 19p13.2 from 7.8 to 18.2 degrees Mbp, a maximum 2-point LOD score of 3.08 was obtained for the marker D19S586. The region overlaps with the recessive locus DFNB15. CONCLUSION: The results underline the heterogeneity of hereditary hearing disorders. Identification of genes can help to reach a better understanding of the molecular mechanism of hearing.

[The "Muenster classification" of high frequency hearing loss following cisplatin chemotherapy]. / Die "Münsteraner Klassifikation": Eine neue Einteilung der Hochtonschwerhörigkeit nach Cisplatingabe.

BACKGROUND: Slight high frequency hearing loss following cisplatin chemotherapy can be proof of an ototoxic effect even when hearing ability is not yet clinically affected. To answer scientific questions, such as the relationship between cisplatin ototoxicity and drug regime or individual tolerance, early detection of ototoxicity and a classification relating to intensity and the affected frequencies are required. A search for relevant literature resulted the WHO-classification (1991) describing clinically relevant hearing loss and two high frequency hearing loss classifications published by Khan et al. (1982) and Brock et al. (1991). Their application is compared to a new, proprietary classification. PATIENTS AND METHODS: 55 patients (32 boys, 23 girls) undergoing cisplatin chemotherapy at Muenster University Hospital from 1999 to 2004 underwent audiometric tests in our department. From this data we developed a grading system, that was based on the WHO classification, but paid special attention to early ototoxic effects, to intensity of hearing loss and to the frequencies affected: Grade 0 (normal hearing) includes hearing loss of not more than 10 dB in all frequencies. Grade 1 (beginning hearing loss) encompasses > 10 dB up to 20 dB in at least one frequency or tinnitus. Grade 2 (moderate impairment) describes hearing loss > or = 4 kHz and differentiates 2a (> 20 to 40 dB), 2b (> 40 to 60 dB) and 2c (> 60 dB). Hearing loss < 4 kHz > 20 dB in grade 3 (severe impairment, hearing aids needed) is further classified according to grade 2 in a, b and c. Grade 4 (loss of function) finally describes average hearing loss < 4 kHz of at least 80 dB. This classification is compared to the two high frequency hearing loss classifications (Khan et al. and Brock et al.). RESULTS: The Muenster classification, compared to Khan et al. and Brock et al., demonstrated the best results in the early detection of hearing loss: All children with hearing loss of at least 20 dB after therapy had already shown pathological audiograms during treatment, when those audiograms were assessed by our classification. All children whose audiograms were flagged as pathological by our classification finally developed hearing loss. In terms of the prediction of hearing loss, our classification evaluated processing audiograms with a sensitivity, specificity and efficiency of 1.0. Progressive hearing loss was detected in 45 patients (Khan et al. 30, Brock et al. 38). Therefore our classification showed a better suitability for monitoring hearing loss than the other classifications. CONCLUSION: The Muenster classification is a suitable new basis for scientific questions concerning cisplatin ototoxicity. It detects hearing loss earlier and maps progression of hearing loss more precisely than the existing high frequency classifications (Khan et al. and Brock et al.).

[Cisplatin-induced hearing loss in children in relation to eye color]. / Cisplatininduzierte Hörstörungen bei Kindern in Abhängigkeit von der Pigmentierung der Iris.

BACKGROUND: Cisplatin is commonly used as a chemotherapeutic agent in the treatment of solid tumors. Ototoxicity is an important side-effect. Melanin in the inner ear either plays an otoprotective role or has a negative influence on hearing. The concentration of cochlear melanin correlates with its concentration in the iris. PATIENTS AND METHODS: We retrospectively examined 65 children (37 males, 28 females, average age 7.5 years) treated with cisplatin at the University Clinic of Muenster, Germany. We checked whether their eye color could be inferred from the prevalence and extent of cisplatin-induced hearing loss. RESULTS: We found a hearing loss of >20 dB in 29 light-eyed and in 21 dark-eyed patients. Seven light-eyed and eight dark-eyed patients did not suffer from hearing impairment. Using the chi(2)-test on these four parameters, we found no significant connection between iris pigmentation and the prevalence or extent of hearing loss, although light-eyed children (80.6%) suffered more from hearing loss than dark-eyed children (72.4%). After the end of therapy with cisplatin, the prevalence of hearing loss was 83.3% in children up to 6 years and 71.4% in children older than 6 years. The average cumulative dose of cisplatin was 372 mg/m(2) of body surface in children with hearing loss, compared to 390 mg/m(2) in children without hearing loss. CONCLUSION: We found no significant correlation between iris pigmentation (eye color) and hearing loss. Cisplatin-induced hearing loss occurs frequently and requires repeated monitoring.

Smoking and IPMN malignant progression.

BACKGROUND: Patients with intraductal papillary mucinous neoplasm (IPMN) are at risk for invasive pancreatic cancer. We aim to characterize the impact of smoking on IPMN malignant progression. METHODS: Patients undergoing pancreatic resection for IPMN (1991-2015) were retrospectively reviewed using a prospectively collected database. RESULTS: Of 422 patients identified, 324 had complete data for analysis; 55% were smokers. Smoking status did not impact IPMN malignant progression (smokers/non-smokers: 22%/18% invasive grade; p = 0.5). Smokers were younger than non-smokers at the time of IPMN diagnosis (63 versus 68 years; p = 0.001). This association also held in the invasive IPMN subgroup (65 versus 72 years, p = 0.01). Despite this observation, rate of symptoms at diagnosis, cancer stage, and median survival were the same between smokers and non-smokers. CONCLUSION: Although smoking is not associated with IPMN malignant progression, invasive IPMN is diagnosed at a younger age in smokers. These data suggest tobacco exposure may accelerate IPMN malignant progression.

Maternal/fetal interactions: the role of the MHC class I molecule HLA-G.

The unique pattern of class I major histocompatibility complex (MHC) antigen expression seen at the human maternal/fetal interface is thought to be vital for fetal well-being. The lack of polymorphic class I and II MHC antigens on trophoblasts, the only fetal tissue in direct contact with the mother, is likely to be at least a part of the explanation of fetal evasion of allograft rejection. The recent observation that the HLA-G-encoded class I MHC molecule is present on certain subpopulations of cytotrophoblasts suggests that this nonpolymorphic molecule may have a role in the maternal/fetal immune response. Although no experimental evidence exists to support a particular function for HLA-G, reasoned speculation about the possible roles of this nonpolymorphic class I molecule is possible. Data derived from sequence analysis, analysis of HLA-G expression patterns, analysis of the extraembryonic expression patterns of other genes, and analysis of decidual lymphocyte phenotype and function provide insight into the possible functions of HLA-G at the maternal/fetal interface and are considered here.