Intercepting the Intussusception: A Rare Case of Adult Intussusception With a Cecal Neuroendocrine Tumor Lead Point.

Intussusception is the invagination of one segment of the bowel into the adjacent bowel segment leading to obstruction, intestinal ischemia and, in severe cases, peritonitis and perforation. While the condition is more common in children, adult intussusception does occur and is often attributed to malignancy. In this case report, we discuss an adult man who presented for weight loss and intermittent abdominal pain and was ultimately found to have ileocecal intussusception on CT imaging. A colonoscopy with cold biopsy was performed and pathology reports displayed a well-differentiated neuroendocrine tumor lead point; a rare event with only a few cases reported. Ultimately, the patient was taken to the operating room, and an ileocecectomy was performed with primary anastomosis. Prompt diagnosis and management are crucial in adult intussusception as a missed event can lead to tumor progression, bowel ischemia, bleeding and necrosis.

A Simple Vitamin Deficiency With Life-Threatening Complications: A Case of B12 Deficiency and Hyperhomocysteinemia-Induced Thrombosis.

While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12 deficiency, and this is linked to thrombus formation with potentially life-threatening complications. We present a patient with severe vitamin B12 deficiency complicated by hyperhomocysteinemia and obstructive shock from pulmonary embolism. A 56-year-old male with no medical history presented to the hospital with altered mentation. The patient's family stated he was experiencing bilateral paresthesias of his lower extremities, progressive depression, anxiety, and insomnia. Initial vitals were blood pressure of 76/36, heart rate of 70 beats per minute, respiratory rate of 14, and temperature of 36.3 degrees Celsius. He was intubated due to severe encephalopathy. Relevant labs indicated severe macrocytic anemia, thrombocytopenia, decreased B12 levels, elevated methylmalonic acid, and elevated homocysteine. Imaging demonstrated a right common femoral vein thrombosis and subsegmental pulmonary emboli. Peripheral blood smear revealed schistocytes, anisopoikilocytosis, and decreased platelet count. The patient required fluid resuscitation, antibiotics, and multiple blood products. Vitamin B12 was administered intramuscularly, which improved the anemia. Esophagogastroduodenoscopy (EGD) demonstrated gastritis. Gastric and duodenal biopsies were negative for Helicobacter pylori and celiac disease. He was negative for intrinsic factor (IF) antibodies but had elevated gastrin levels. An intravenous unfractionated heparin infusion was started when the platelet count was above 50000. The patient was extubated after seven days. Heparin was transitioned to apixaban and an inferior vena cava (IVC) filter was placed. Hyperhomocysteinemia is a known pro-thrombotic factor that can lead to the development of venous thromboembolism. B12 malabsorption can stem from inflammatory bowel disease, celiac disease, gastritis, pancreatic insufficiency, gastrectomy, gastric bypass surgery, or antibodies to IF. While this case showed gastritis and negative IF antibodies, gastrin levels were elevated, indicating a mixed picture. This highlights the challenge of definitively diagnosing pernicious anemia as the cause of vitamin B12 deficiency. Vitamin B12 deficiency may lead to critical illness in which thromboembolism develops secondary to hyperhomocysteinemia.

No Stone Left Unturned: Bouveret Syndrome Treated With Electrohydraulic Lithotripsy and Open Extraction With Pyloric Exclusion and Gastrojejunostomy.

Bouveret syndrome is ectopic gallstone impaction and obstruction of the duodenum or pylorus affecting a small minority of gallstone ileus cases. There have been advances in its endoscopic management, but this remains a challenging condition to treat successfully. We present a patient with Bouveret syndrome who required open surgical extraction and gastrojejunostomy after attempts of endoscopic retrieval and electrohydraulic lithotripsy (EHL). A 79-year-old man with a medical history of gastroesophageal reflux disease, chronic obstructive pulmonary disease on 5 liters of oxygen at baseline, and coronary artery disease with recent stenting presented to the hospital with three days of abdominal pain and vomiting. CT of the abdomen/pelvis demonstrated gastric outlet obstruction, a 4.5 cm gallstone in the proximal duodenum, cholecystoduodenal fistula, gallbladder wall thickening, and pneumobilia. Esophagogastroduodenoscopy (EGD) demonstrated a black pigmented stone impacted in the duodenal bulb with ulceration of the inferior wall. Repeated Roth net retrieval attempts of the stone were unsuccessful even after biopsy forceps were used to trim the stone's margins. The next day, EGD with EHL used 20 shocks of 200 watts, allowing for partial stone removal and fragmentation, but the majority of the stone remained stuck to the wall. Laparoscopic cholecystectomy was attempted but was converted to an open extraction of the gallstone from the duodenum, pyloric exclusion, and gastrojejunostomy. The gallbladder remained in place, and the cholecystoduodenal fistula was not surgically repaired. The patient experienced significant postoperative pulmonary insufficiency and remained on the ventilator with failure of multiple spontaneous breathing trials. Postoperative imaging showed resolution of pneumobilia but a small amount of contrast leaked from the duodenum revealing the fistula's persistence. After 14 days of unsuccessful ventilator weaning, the family opted for palliative extubation. Advanced endoscopic techniques have been regarded as the first-line intervention for Bouveret syndrome as there is low morbidity and mortality associated with them. However, there is a reduced success rate compared to surgical intervention. Open surgical management has high morbidity and mortality in the elderly and comorbid patients commonly affected by this condition. Thus, the risks and benefits must be weighed and individualized for each patient with Bouveret syndrome before therapeutic intervention.

Addressing Single Nuclear Spins Quantum Memories by a Central Electron Spin.

Nuclei surrounding single electron spins are valuable resources for quantum technology. For application in this area, one is often interested in weakly coupled nuclei with coupling strength on the order of a few 10-100 kHz. In this paper, we compare methods to address single nuclear spins with this type of hyperfine coupling to a single electron spin. To achieve the required spectral resolution, we specifically focus on two methods, namely dynamical decoupling and correlation spectroscopy. We demonstrate spectroscopy of two single nuclear spins and present a method to derive components of their hyperfine coupling tensor from those measurements.

Myers-Briggs Type Indicator Personality Types of Female Intern Doctors and Their Specialty Preference.

The Myers-Briggs Type Indicator (MBTI) personality types were established in 1940s. Career planning of doctors were found related to the MBTI personality. There are 16 subtypes of MBTI based on 4 dichotomies. Relationship between MBTI and career choice has been changed gradually in last few decades. Extroverted doctors are supposed to select surgery and introverted are prone to choose medicine according to MBTI study. This was a cross-sectional study on the female interns of Sylhet Women's Medical College Hospital, Bangladesh from September 2021 to November 2021, to evaluate their MBTI personality type and the career planning of these individual subtypes. Commonest subtypes of participants ISTP (Introverted, Sensing, Thinking, Perceiving) (14.13%) and ESTP (Extraverted, Observant, Thinking and Prospecting) (14.13%). Other common MBTI personality subtypes were ISTJ (Introversion, Sensing, Thinking and Judgment) (9.78%), ISFP (Introverted, Sensing, Feeling, Perceiving) (8.69%), ESFJ (Extraverted, Sensing, Feeling and Judging) (6.52%), ENTP (Extraverted, Intuitive, Thinking and Perceiving) (5.43%), INFJ (Introverted, Intuitive, Feeling and Judging) (5.43%), INTJ (Introverted, Intuitive, Thinking and Judging) (5.43%) and ISFJ (Introverted, Sensing, Feeling and Judging) (5.43%). Introverted (57.7%) participants were more than extroverted (42.3%) participants. Percentage of general surgery and OBG were higher in the extroverted group and the percentage of medicine was more in the introverted group but the differences were not statistically significant (p>0.05). The career planning of ENFJ, ENFP, ESTP and ISTJ subtypes of participants of this study had similarity of those of MBTI database.

Study protocol of the FIRE-8 (AIO-KRK/YMO-0519) trial: a prospective, randomized, open-label, multicenter phase II trial investigating the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer.

BACKGROUND: Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/ tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/ tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches. METHODS: FIRE-8 ( NCT05007132 ) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m2 body surface area (BSA), orally twice daily on days 1-5 and 8-12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled. DISCUSSION: To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy. TRIAL REGISTRATION: EU Clinical Trials Register (EudraCT) 2019-004223-20 . Registered October 22, 2019, ClinicalTrials.gov NCT05007132 . Registered on August 12, 2021.

High rate of autonomic neuropathy in Cornelia de Lange Syndrome.

BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence. METHOD: Somatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained. RESULTS: Sympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies. CONCLUSIONS: Autonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange Syndrome, and could be related to premature aging.

Cross-Sectional Analytic Study to Compare the Efficacy Between of Clinical Skill Learning (CSL) and Multimedia Lecture as Teaching Tool in Case of Endotracheal Intubation.

Clinical skill lab (CSL) is a part of simulation-based medical education (SBME) which now a days becomes an integral part of modern medical education. This cross-sectional analytic study was performed at Sylhet Women's Medical College, Sylhet, Bangladesh to assess the difference between CSL and traditional multimedia (MM) presentation in case of endotracheal intubation from January 2021 to February 2021. Total 78 first year nursing students were enrolled in study. Both groups were tested by same pre-tested multiple-choice questions. These 10 questions were set according to modified bloom's taxonomy domains. There was no significant difference in the mean scores of both groups. Male of CSL group had scored significantly better than the female of the same group. The top and bottom domains of modified bloom's taxonomy were significantly better taught in CSL group, whereas the others were better in the multimedia group.

Animal-derived medications: cultural considerations and available alternatives.

CONTEXT: Cultural competency is a cornerstone of patient-centered health care. Religious doctrines may define appropriate consumption or use of certain animals and forbid use of others. Many medications contain ingredients that are animal-derived; these medications may be unacceptable to individual patients within the context of their religious beliefs and lifestyle choices. Knowledge of animal-derived medications as a component of cultural competency can facilitate a dialogue that shifts focus from the group to the individual, away from cultural competency toward cultural humility, and away from a paternalistic provider/patient dynamic toward one of partnership. OBJECTIVES: To explore how animal-derived drug components may impact medication selection and acceptability from the perspective of patients, physicians, and religious leaders as evidenced by studies that explore the question via survey or questionnaire. A secondary objective is to use the context of animal-derived drug products as a component of cultural competency to build a framework supporting the development of cultural humility. METHODS: A systematic search was performed in the PubMed, CINAHL, Cochrane, and ProQuest databases using combinations of the following terms: "medication selection," "medication," "adherence," "pharmaceutical preparations," "religion and medicine," "religion," "animal," "dietary," "porcine," and "bovine." Studies that reported using surveys or questionnaires to examine patient, physician, or religious leader perspective on animal-derived medications published in English between 1990 and 2020 were included. Review articles, opinion pieces, case reports, surveys of persons other than patients, religious leaders, or physicians, and studies published in languages other than English were excluded. Three authors independently reviewed articles to extract information pertaining to perspectives on animal-based medication ingredients. RESULTS: Eight studies meeting the described criteria were found that queried beliefs or knowledge of patients, religious leaders, or physicians regarding medications and medical products of biologic origin. Those studies are described in full in this review. CONCLUSIONS: Knowledge of animal-derived ingredients may help open conversations with patients around spiritual history and cultural competency, particularly for those patients belonging to religious sects with doctrines that define appropriate use of human- or animal-derived products. Further formal study is needed to explore more fully the extent to which religious beliefs may impact selection of animal- or human-derived medications. Guidelines developed from this knowledge may aid in identifying individual patients with whom the discussion may be particularly relevant. More studies are needed to quantify and qualify beliefs regarding animal-derived medication constituents.

Afatinib plus gemcitabine versus gemcitabine alone as first-line treatment of metastatic pancreatic cancer: The randomised, open-label phase II ACCEPT study of the Arbeitsgemeinschaft Internistische Onkologie with an integrated analysis of the 'burden of therapy' method.

BACKGROUND: Targeting the epidermal growth factor receptor pathway remains controversial in pancreatic cancer. Afatinib is an oral irreversible ErbB family blocker approved in non-small-cell lung cancer. This open-label, multicenter, randomised phase II trial evaluated gemcitabine plus afatinib (Gem/afatinib) versus gemcitabine (Gem) alone as first-line treatment for metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomised in a 2:1 ratio to either Gem (1000 mg/m2 weekly for three weeks followed by one week of rest, repeated every four weeks) and afatinib (40 mg orally once daily) or Gem alone. Overall survival (OS) was the primary study end-point. The novel BOTh©™ methodology was implemented to derive a quantitative estimate for the 'Burden of Therapy/Toxicity' (BOTh) for each patient on every day during the clinical study. RESULTS: One hundred nineteen patients from 25 centres were randomised, 79 patients for Gem/afatinib and 40 for Gem. Median OS was 7.3 months in the Gem/afatinib arm versus 7.4 months in the Gem-alone arm (hazard ratio [HR]: 1.06, p = 0.80). Median progression-free survival was identical in both arms (3.9 months versus 3.9 months, HR: 0.85, p = 0.43). Adverse events were more frequent in the Gem/afatinib arm, especially diarrhoea (71% vs. 13%) and skin rash (65% vs. 5%). The BOTh©™ analysis revealed a significantly higher burden of toxicity in the combination arm (p = 0.0005). CONCLUSION: The addition of afatinib to Gem did not improve treatment efficacy and was more toxic. The BOTh©™ methodology allowed a detailed insight into the course of treatment-related adverse events over the study period. The trial was registered at clinicaltrials.gov (NCT01728818) and Eudra-CT (2011-004063-77).

Relation of cetuximab-induced skin toxicity and early tumor shrinkage in metastatic colorectal cancer patients: results of the randomized phase 3 trial FIRE-3 (AIO KRK0306).

BACKGROUND: Cetuximab-induced skin toxicity (Cet-ST) is positively associated with outcome in metastatic colorectal cancer (mCRC). Besides its predictive relevance for targeted therapy, we investigated its prognostic impact with early tumor shrinkage (ETS) ≥20%, another on-treatment surrogate for clinical outcome in FIRE-3. PATIENTS AND METHODS: FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumors (i.e. wild-type in KRAS and NRAS exons 2-4). Retrospective data on Cet-ST that occurred during cycles 1-3 of treatment were correlated with efficacy endpoints, including ETS. To control for guarantee-time bias, only patients who had completed three or more treatment cycles were considered. RESULTS: Of 199 patients treated with FOLFIRI/Cet, 181 (91.0%) completed three or more treatment cycles. A significant survival benefit of FOLFIRI/Cet over FOLFIRI/Bev was only evident in patients developing Cet-ST grade 2-3 [41.0 versus 26.6 months; hazard ratio (HR) = 0.73; 95% confidence interval (CI): 0.61-0.87; P < 0.001] compared with Cet-ST grade 0-1 (HR = 0.90; 95% CI: 0.67-1.20; P = 0.48). Regarding prognosis, Cet-ST grade 2-3 (n = 75; 41.4%), compared with Cet-ST grade 0-1 (n = 106; 58.6%), was associated with prolonged overall survival (OS; HR = 0.62; 95% CI: 0.42-0.91; P = 0.01). In multivariate analysis, both Cet-ST (HR = 0.66; 95% CI: 0.50-0.87; P = 0.003) and ETS (HR = 0.55; 95% CI: 0.41-0.74; P < 0.0001) were independently prognostic for OS. Absence of both Cet-ST grade ≥2 and ETS identified a subgroup of patients with very poor prognosis (median OS 15.1 months). CONCLUSIONS: In FIRE-3, the addition of cetuximab to FOLFIRI was associated with superior OS compared with FOLFIRI/Bev only in patients developing Cet-ST grade ≥2. Regarding prognostic relevance, both Cet-ST and ETS were independent and early predictors of survival. The present analysis supports that a combined evaluation of on-treatment parameters such as Cet-ST and ETS may help to guide treatment of mCRC.

Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial.

BACKGROUND: FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The consensus molecular subgroups (CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of CMS for the treatment of mCRC has yet to be defined. PATIENTS AND METHODS: In this exploratory analysis, patients were grouped according to the previously published tumor CRC-CMSs. Objective response rates (ORR) were compared using chi-square test. Overall survival (OS) and progression-free survival (PFS) times were compared using Kaplan-Meier estimation, log-rank tests. Hazard ratios (HR) were estimated according to the Cox proportional hazard method. RESULTS: CMS classification could be determined in 438 out of 514 specimens available from the intent-to-treat (ITT) population (n = 592). Frequencies for the remaining 438 samples were as follows: CMS1 (14%), CMS2 (37%), CMS3 (15%), CMS4 (34%). For the 315 RAS wild-type tumors, frequencies were as follows: CMS1 (12%), CMS2 (41%), CMS3 (11%), CMS4 (34%). CMS distribution in right- versus (vs) left-sided primary tumors was as follows: CMS1 (27% versus 11%), CMS2 (28% versus 45%), CMS3 (10% versus 12%), CMS4 (35% versus 32%). Independent of the treatment, CMS was a strong prognostic factor for ORR (P = 0.051), PFS (P < 0.001), and OS (P < 0.001). Within the RAS wild-type population, OS observed in CMS4 significantly favored FOLFIRI cetuximab over FOLFIRI bevacizumab. In CMS3, OS showed a trend in favor of the cetuximab arm, while OS was comparable in CMS1 and CMS2, independent of targeted therapy. CONCLUSIONS: CMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making.The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.

Palliative home care for patients with advanced haematological malignancies-a multicenter survey.

Patients with advanced haematological malignancies in non-curative settings suffer from complex physical symptoms and psychosocial distress, comparable to patients with solid tumour entities. Nevertheless, numerous problems at the interface between haematology and palliative home care have been described. From January 2011 until October 2014, we performed a retrospective, multicenter analysis of all patients with haematological malignancies (ICD 10: C81-C95) being treated by the respective specialized palliative home care (SAPV) team. Three SAPV teams were surveyed. Disease entity, physical symptoms, psychosocial distress, number of hospital admissions, therapeutic interventions and other items were analysed descriptively. Of 3,955 SAPV patients, 1.8% (n = 73) suffered from haematological malignancies. Main problems were deterioration of general condition, pain or psychological problems. Thirty-seven percent developed new symptoms during SAPV, mainly pain, psychological distress or deterioration of general status. In 33%, patients were referred to hospital, mainly due to deterioration of general condition or pain. Seventy percent died within 3 months after beginning SAPV care; 83% died at home or in a nursing home. Patients suffering from advanced haematological malignancies were statistically underrepresented in SAPV, and SAPV was installed rather at the very last days of life. By far, more patients were able to die outside a hospital as compared to reference cohorts of haematological patients not being treated in SAPV. The spectrum of documented problems is comparable to other patient cohorts being treated in SAPV; therefore, the options and benefits of palliative home care should be incorporated in palliative haematological treatment concepts more vigorously and consequently.

High quality entanglement on a chip-based frequency comb.

We report an efficient energy-time entangled photon-pair source based on four-wave mixing in a CMOS-compatible silicon photonics ring resonator. Thanks to suitable optimization, the source shows a large spectral brightness of 400 pairs of entangled photons /s/MHz for 500 µW pump power, compatible with standard telecom dense wavelength division multiplexers. We demonstrate high-purity energy-time entanglement, i.e., free of photonic noise, with near perfect raw visibilities (> 98%) between various channel pairs in the telecom C-band. Such a compact source stands as a path towards more complex quantum photonic circuits dedicated to quantum communication systems.

Expanding the clinical spectrum of the 'HDAC8-phenotype' - implications for molecular diagnostics, counseling and risk prediction.

Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction.

Broadening of cohesinopathies: exome sequencing identifies mutations in ANKRD11 in two patients with Cornelia de Lange-overlapping phenotype.

Cornelia de Lange syndrome (CdLS) and KBG syndrome are two distinct developmental pathologies sharing common features such as intellectual disability, psychomotor delay, and some craniofacial and limb abnormalities. Mutations in one of the five genes NIPBL, SMC1A, SMC3, HDAC8 or RAD21, were identified in at least 70% of the patients with CdLS. Consequently, additional causative genes, either unknown or responsible of partially merging entities, possibly account for the remaining 30% of the patients. In contrast, KBG has only been associated with mutations in ANKRD11. By exome sequencing we could identify heterozygous loss-of-function mutations in ANKRD11 in two patients with the clinical diagnosis of CdLS. Both patients show features reminiscent of CdLS such as characteristic facies as well as a small head circumference which is not described for KBG syndrome. Patient A, who carries the mutation in a mosaic state, is a 4-year-old girl with features reminiscent of CdLS. Patient B, a 15-year-old boy, shows a complex phenotype which resembled CdLS during infancy, but has developed to a more KBG overlapping phenotype during childhood. These findings point out the importance of screening ANKRD11 in young CdLS patients who were found to be negative for mutations in the five known CdLS genes.

Scleredema. A multicentre study of characteristics, comorbidities, course and therapy in 44 patients.

BACKGROUND: The prognostic and therapeutic features of scleredema are poorly documented. OBJECTIVES: To describe the characteristics of patients with scleredema regarding demographics, clinical characteristics, comorbidities, therapeutic interventions and course. METHODS: We conducted a retrospective multicentre study. RESULTS: We identified 44 patients (26 men).The mean age at diagnosis was 53.8 years. The most common associated disorders were endocrine/metabolic diseases including 30 patients suffering from diabetes, mostly type 2 diabetes. Monoclonal gammopathies were confirmed in five cases. A preceding respiratory tract infection was not a feature. Treatments with different combination or sequential modalities were used with variable results. Phototherapy (UVA1 or PUVA) was the treatment associated with higher, although partial response. Systemic corticosteroids and immunosuppressive drugs were reserved to patients with severe disease in whom phototherapy had failed or for patients with multiple myeloma. Forty-one patients were followed up (mean period: 32.2 months).Thirty-nine patients are alive, 30 with and 9 without skin disease. Two patients died of cardiovascular complications due to myeloma and severe diabetes. CONCLUSIONS: Scleredema is a chronic debilitating disease associated with diabetes and metabolic syndrome, unresponsive to various treatments but not necessarily a life-threatening condition. Although there is no definitive treatment, phototherapy should be attempted first. Treatment of primary disease including strict glycaemic control combined with physical therapy should be also employed.

Identification of a single SNP that affects the promoter activity in the Moroccan prolific D'man breed.

Common Moroccan breeds D'man, Sardi, and Timahdite have been found to differ regarding litter size. D'man is known for its high prolificacy (2-7 lambs), whereas Timahdite and Sardi are normally prolific (1-2 lambs). Here, we aimed to identify genetic variants in the ß promoter and to study the promoter activity amongst these breeds using sequencing for the former and the in vitro luciferase assay for the latter. Sequence analysis revealed 16 genetic variants among these common breeds. Luciferase assay analysis demonstrated a higher promoter activity in D'man compared to the Sardi/Timahdite breeds. A small region of 541 bp was further characterized as possessing a high promoter activity. This region contains 2 palindromic sequences and 7 variants. Based on in silico analysis, only 2 variants at position -559 and -568 were found to be informative. These 2 variants were localized within a region rich in transcription factor binding sites including GATA-1/GATA-2, E4/th1, CP2, and c-Ets. Using site-directed mutagenesis, only the variant at position -559 A/G was found to substantially influence the promoter activity. Taken together, differences in the level of ß transcription among highly and minimally prolific Moroccan breeds were demonstrated and a novel single variant was identified that could explain this difference.

[The Oncologic and Palliative Network Landshut: a problem-solving approach to oncological and palliative care in structurally weak rural areas, with special emphasis on outpatient and inpatient networking]. / Das Onkologische und Palliativmedizinische Netzwerk Landshut. Lösungsansatz für die zukünftige ambulante und stationäre Versorgung von onkologischen und palliativmedizinischen Patienten in strukturschwachen ländlichen Gebieten.

The Oncologic and Palliative Network Landshut is a problem-solving approach to structurally weak rural areas to improve an a dequate care of critically ill patients, especially by a close involvement of outpatient and inpatient care providers. These networks not only improve the medical and nursing care of patients, but can also be cost-effective.

[The Oncologic and Palliative Network Landshut: a problem-solving approach to oncological and palliative care in structurally weak rural areas, with special emphasis on outpatient and inpatient networking]. / Das Onkologische und Palliativmedizinische Netzwerk Landshut. Lösungsansatz für die zukünftige ambulante und stationäre Versorgung von onkologischen und palliativmedizinischen Patienten in strukturschwachen ländlichen Gebieten.

The Oncologic and Palliative Network Landshut is a problem-solving approach to structurally weak rural areas to improve an adequate care of critically ill patients, especially by a close involvement of outpatient and inpatient care providers. These networks not only improve the medical and nursing care of patients, but can also be cost-effective.