First effectiveness data of lenvatinib and pembrolizumab as first-line therapy in advanced anaplastic thyroid cancer: a retrospective cohort study.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare and aggressive neoplasm. We still lack effective treatment options, so survival rates remain very low. Here, we aimed to evaluate the activity of the combination of lenvatinib and pembrolizumab as systemic first-line therapy in ATC. METHODS: In a retrospective analysis, we investigated the activity and tolerability of combined lenvatinib (starting dose 14 to 24 mg daily) and pembrolizumab (200 mg every three weeks) as first-line therapy in an institutional cohort of ATC patients. RESULTS: Five patients with metastatic ATC received lenvatinib and pembrolizumab as systemic first-line therapy. The median progression-free survival was 4.7 (range 0.8-5.9) months, and the median overall survival was 6.3 (range 0.8-not reached) months. At the first follow-up, one patient had partial response, three patients had stable disease, and one patient was formally not evaluable due to interference of assessment by concomitant acute infectious thyroiditis. This patient was then stable for more than one year and was still on therapy at the data cutoff without disease progression. Further analyses revealed deficient DNA mismatch repair, high CD8+ lymphocyte infiltration, and low macrophage infiltration in this patient. Of the other patients, two had progressive disease after adverse drug reactions and therapy de-escalation, and two died after the first staging. For all patients, the PD-L1 combined positive score ranged from 12 to 100%. CONCLUSIONS: The combination of lenvatinib and pembrolizumab was effective and moderately tolerated in treatment-naïve ATC patients with occasional long-lasting response. However, we could not confirm the exceptional responses for this combination therapy reported before in pretreated patients.

Achieving Competency in Fiber-Optic Intubation Among Resident Physicians After Higher- Versus Lower-Fidelity Task Training: A Randomized Controlled Study.

BACKGROUND: The high-fidelity ORSIM (Airway Simulation Ltd) and the low-fidelity wooden-block fiber-optic task trainers allow users to familiarize themselves with the psychomotor skills required to manipulate the fiber-optic scope. METHODS: This single-center study aimed to compare residents' performance of fiber-optic intubation after 2 different types of task training. Twenty-four residents with experience of <8 fiber-optic intubations were randomized to either the ORSIM or a wooden-block task trainer. In a single teaching session, the resident performed 20 fiber-optic intubations on their assigned task trainer. This implied simulator competence. In the 4 months after this training, all subjects then attempted to perform a fiber-optic intubation on an American Society of Anesthesiologists (ASA) I or II anesthetized patient whose airway was preoperatively assessed as normal. The primary outcome was the cumulative sum (CUSUM) learning curves obtained as the residents trained on their respective task trainers. Secondary outcomes included: the mean time (in seconds) to perform each of the 20 fiber-optic intubations on their assigned task trainer, the total simulator training time, global rating scale score, checklist score, and time to carina when performing fiber-optic intubation on the patient. RESULTS: The CUSUM analysis showed that the ORSIM group achieved simulator competence faster. The mean time to perform fiber-optic intubation was shorter in the ORSIM group. A 2-way analysis of variance (ANOVA) test suggests that the combined effect of group (wooden-block or ORSIM) and time is statistically significant ( P < .05).Total training time (mean, 899 s ± 440 s vs 1358 s ± 405 s; 95% confidence interval [CI], 100.46-818.54; P = .01) was also significantly better in the ORSIM group.No significant difference was found between the 2 groups ( P > 0) in terms of global rating scale, checklist score, and time to reach the carina ( P >.05) when performing the fiber-optic intubation on the patient. CONCLUSIONS: ORSIM showed superiority in terms of the CUSUM learning curve in reaching competence faster in fewer attempts. There was no statistically significant difference in residents' performance when translated to clinical practice on a patient. This information should assist course directors when choosing task trainers for fiber-optic intubation training programs.

Prognostic differences in grading and metastatic lymph node pattern in patients with small bowel neuroendocrine tumors.

PURPOSE: Neuroendocrine tumors of the small intestine (si-NET) describe a heterogenous group of neoplasms. Based on the Ki67 proliferation index si-NET are divided into G1 (Ki67 < 2%), G2 (Ki67 3-20%) and rarely G3 (Ki67 > 20%) tumors. However, few studies evaluate the impact of tumor grading on prognosis in si-NET. Moreover, si-NET can form distinct lymphatic spread patterns to the mesenteric root, aortocaval lymph nodes, and distant organs. This study aims to identify prognostic factors within the lymphatic spread patterns and grading. METHODS: Demographic, pathological, and surgical data of 208 (90 male, 118 female) individuals with si-NETs treated at Charité University Medicine Berlin between 2010 and 2020 were analyzed retrospectively. RESULTS: A total of 113 (54.5%) specimens were defined as G1 and 93 (44.7%) as G2 tumors. Interestingly, splitting the G2 group in two subgroups: G2 low (Ki67 3-9%) and G2 high (Ki67 10-20%), displayed significant differences in overall survival (OS) (p = 0.008) and progression free survival (PFS) (p = 0.004) between these subgroups. Remission after surgery was less often achieved in patients with higher Ki67 index (> 10%). Lymph node metastases (N +) were present in 174 (83.6%) patients. Patients with isolated locoregional disease showed better PFS and OS in comparison to patients with additional aortocaval and distant lymph node metastases. CONCLUSION: Lymphatic spread pattern influences patient outcome. In G2 tumors, low and high grading shows heterogenous outcome in OS and PFS. Differentiation within this group might impact follow-up, adjuvant treatment, and surgical strategy.

CHANGES IN SYSTEMIC LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AFTER INTRAVITREAL INJECTION OF AFLIBERCEPT OR BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To analyze and compare the effects of intravitreal brolucizumab versus aflibercept on systemic vascular endothelial growth factor (VEGF)-A levels in patients with neovascular age-related macular degeneration. METHODS: In this prospective interventional case series study, brolucizumab (6.0 mg/50 µL) or aflibercept (2.0 mg/50 µL) was injected intravitreally in 30 patients each. Blood samples were drawn at baseline and 7 days and 28 days after the first injection. Systemic VEGF-A levels were measured using enzyme-linked immunosorbent assay. Thirty healthy individuals served as controls. RESULTS: The median baseline systemic VEGF-A levels in the brolucizumab, aflibercept, and control groups were 10.8 (8.0-13.2), 12.0 (8.0-18.5), and 10.0 (8.0-15.1) pg/mL, respectively (P = 0.315). In the brolucizumab group, VEGF-A levels significantly decreased to 8.0 (8.0-11.5) pg/mL on Day 7 (P = 0.0254) and to 8.0 (8.0-8.0) pg/mL on Day 28 (P < 0.001). In the aflibercept group, VEGF-A levels significantly decreased to 8.0 (8.0-8.0) pg/mL on Day 7 (P < 0.001) but returned to the baseline level, 12.5 (8.5-14.6) pg/mL, on Day 28 (P = 0.120). Vascular endothelial growth factor-A levels were significantly different between the treatment groups after 28 days (P < 0.001). CONCLUSION: Intravitreal brolucizumab resulted in a sustained reduction of systemic VEGF-A levels until 28 days posttreatment, which raises concerns regarding its safety and long-term effects.

[Differentiated Strategies for the Therapy of Liver Metastases in Gastro-entero-pancreatic Neuroendocrine Neoplasia]. / Differenzierte Therapiestrategie bei Lebermetastasen gastro-entero-pankreatischer Neuroendokriner Neoplasien.

Neuroendocrine neoplasias comprise a heterogenous group of malignant tumours, mostly arising from the gastro-entero-pancreatic system (GEP). Most of these tumours develop from the small intestine and pancreas and the liver is the predominant site for distant metastases. Patients may be asymptomatic for a long time and liver metastases are frequently diagnosed by chance or during operations for bowel obstruction, for example, during emergency surgery. The only curative therapy consists in complete removal of primary and metastases. In case of metastatic disease, various treatment modalities need to be discussed in interdisciplinary tumour boards comprised of specialists from gastroenterology, (liver-)surgery, radiology, nuclear medicine, radiotherapy, pathology and endocrinology. By combining different therapies, even patients with progressive disease may reach long-term overall survival with good quality of life. The most important factors for decisions on therapy are individual factors like tumour grading, hormonal functionality, type of metastases and evolution of the disease. Adequate treatment of liver metastases comprises various surgical strategies as well as locally ablative radiological interventions and nuclear medical therapies, in complement to systemic treatments.

Racial Differences in a Detroit, MI, ICU Population of Coronavirus Disease 2019 Patients.

OBJECTIVES: To investigate the potential influence of racial differences in outcomes of patients infected by coronavirus disease 2019-positive patients who require intensive care in an urban hospital. DESIGN: Retrospective cohort study. SETTING: Henry Ford Health System Multidisciplinary ICU, a total of 156 beds spread throughout the hospital in Detroit, MI. PATIENTS: We obtained data from the electronic medical record of all adult severe acute respiratory syndrome coronavirus-2-positive patients managed in the ICU of Henry Ford Hospital in Detroit, MI, between March 13, 2020, and July 31, 2020. Included patients were divided into two groups: people of color (including Black, Asian, Hispanic/Latino, and Arab) and White. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 365 patients were evaluated: 219 were Black (60.0%), 129 were White (35.3%), two were Asian (0.6%), eight were Hispanic/Latino (2.2%), and seven were Arab (1.9%). People of color were younger (62.8 vs 67.1; p = 0.007), with equal distribution of sex. People of color had less coronary artery disease (34 [14.4%] vs 35 [27.1%]; p =0.003) and less self-reported use of regular alcohol consumption (50 [21.2%] vs 12 [9.3%]; p = 0.004) than Whites, with no differences in diabetes (125 [53.0%] vs 66 [51.2%]; p = 0.742), hypertension (188 [79.7%] vs 99 [76.8%]; p = 0.516), congestive heart failure (41 [17.4%] vs 32 [24.8%]; p = 0.090), or chronic kidney disease (123 [54.1%] vs 55 [42.6%]; p = 0.083).There was no difference in ICU length of stay between people of color (18 d [CI, 7-47 d]) and Whites (18 d [CI, 6-48 d]; p = 0. 0.979). Neither frequency (72.5% vs 71.3%; p = ns) nor median time to mechanical ventilation between people of color (9 d [CI, 6-15 d]) and Whites (10 d [CI, 5-16 d]; p = 0.733) was different. Overall, 188 patients (51.5 %) died in the hospital. The 28-day mortality was lower in people of color (107/236; 45.3%) versus Whites (73/129; 56.6%) (adjusted odds ratio 0.60; p = 0.034), and there was an increased median survival time in people of color (20 d) versus Whites (13.5 d; hazard ratio 0.62; p = 0.002). The inhospital mortality was lower in people of color versus White, but the difference was not statistically significant (113 [47.9%] vs 75 [58.1%], respectively; p = 0.061). Finally, there was no significant difference in days of symptoms prior to admission, frequency of presenting symptoms, or frequency or severity of acute respiratory distress syndrome between the two groups. CONCLUSIONS: In critically ill patients infected with coronavirus disease 2019, people of color had a lower 28-day mortality than Whites with no difference in hospital mortality, ICU length of stay, or rates of intubation. These findings are contrary to previously held beliefs surrounding the pandemic.

"They're Doing Their Job": Women's Acceptance of Emergency Department Contraception Counseling.

STUDY OBJECTIVE: We explore reproductive-aged women's acceptance of contraception counseling in the emergency department (ED). METHODS: This study is phase 1 of an exploratory sequential mixed methods study. We purposively interviewed 31 participants with the following criteria: black, white, or Latina race/ethnicity; nonpregnant; aged 15 to 44 years; receiving nonemergency care; not using highly effective contraception; and did not intend to become pregnant. We conducted semistructured interviews with a piloted interview guide until reaching thematic saturation. We coded transcripts with an iteratively developed codebook, maintaining intercoder agreement greater than 80%. Qualitative acceptance of ED contraception counseling was grouped into 3 categories: acceptable, unacceptable, and equivocal. We conducted a thematic text analysis to assess themes expressing support and concern for ED contraception counseling. Qualitative findings were stratified by age, race, and frequency of ED use. Using components of grounded theory, we developed a conceptual model. RESULTS: Most participants (81%) accepted ED contraception counseling. Themes expressing support and concern for ED contraception counseling included opportunity to address women's unmet contraception needs, contraception is within the scope of ED practice, the ED is a convenient setting with competent providers, contraception is a sensitive topic, and the ED may be an inappropriate setting for some women. Latina participants had lower acceptance of ED contraception counseling. Dominant subthemes varied slightly by race, age, and frequency of ED use. CONCLUSION: Diverse women had high acceptance of contraception counseling in the ED. Perspectives expressing both support and concern in regard to ED contraception counseling were explored in detail.

Development of an ontology for laparoscopic transabdominal adrenalectomy via a comprehensive modified Delphi survey and its validation on a multicentric pilot data set for surgical training and future video analysis with machine learning algorithms.

Surgical technique is essential to ensure safe minimally invasive adrenalectomy. Due to the relative rarity of adrenal surgery, it is challenging to ensure adequate exposure in surgical training. Surgical video analysis supports auto-evaluation, expert assessment and could be a target for automatization. The developed ontology was validated by a European expert consensus and is applicable across the surgical techniques encountered in all participating centres, with an exemplary demonstration in bi-centric recordings. Standardization of adrenalectomy video analysis may foster surgical training and enable machine learning training for automated safety alerts.

Curative and palliative surgery in patients with neuroendocrine tumors of the gastro-entero-pancreatic (GEP) tract.

The incidence of neuroendocrine tumors (NET) increases with age. Lately, the diagnosis of NET was mainly caused by early detection of small NET (<1 cm) in the rectum and stomach, which are depicted by chance during routine and prophylactic endoscopy. Also in patients with large and metastatic pancreatic and intestinal tumors thorough pathologic investigation with use of different immunohistologic markers discovers more neuroendocrine tumors with low differentiation grade (G2-G3) and more neuroendocrine carcinomas (NEC), nowadays, than in former times. While gastric and rectal NET are discovered as small (<1 cm in diameter) and mainly highly differentiated tumors, demonstrating lymph node metastases in less than 10% of the patients, the majority of pancreatic and small bowel NET have already metastasized at the time of diagnosis. This is of clinical importance, since tumor stage and differentiation grade not only influence prognosis but also surgical procedure and may define whether a combination of surgery with systemic biologic therapy, chemotherapy or local cytoreductive procedures may be used. The indication for surgery and the preferred surgical procedure will have to consider personal risk factors of each patient (i.e. general health, additional illnesses, etc.) and tumor specific factors (i.e. tumor stage, grade of differentiation, functional activity, mass and variety of loco regional as well as distant metastases etc.). Together they define, whether radical curative or only palliative surgery can be applied. Altogether surgery is the only cure for locally advanced NET and helps to increase quality of life and overall survival in many patients with metastatic neuroendocrine tumors. The question of cure versus palliative therapy sometimes only can be answered with time, however. Many different aspects and various questions concerning the indication and extent of surgery and the best therapeutic procedure are still unanswered. Therefore, a close multidisciplinary cooperation of colleagues involved in biochemical and localization diagnostics and those active in various treatment areas is warranted to search for the optimal strategy in each individual patient. How far genetic screening impacts survival remains to be seen. Since surgeons do have a central role in the treatment of NET patients, they have to understand the need for integration into such an interdisciplinary team.

Teledermatology: Comparison of Store-and-Forward Versus Live Interactive Video Conferencing.

A decreasing number of dermatologists and an increasing number of patients in Western countries have led to a relative lack of clinicians providing expert dermatologic care. This, in turn, has prolonged wait times for patients to be examined, putting them at risk. Store-and-forward teledermatology improves patient access to dermatologists through asynchronous consultations, reducing wait times to obtain a consultation. However, live video conferencing as a synchronous service is also frequently used by practitioners because it allows immediate interaction between patient and physician. This raises the question of which of the two approaches is superior in terms of quality of care and convenience. There are pros and cons for each in terms of technical requirements and features. This viewpoint compares the two techniques based on a literature review and a clinical perspective to help dermatologists assess the value of teledermatology and determine which techniques would be valuable in their practice.

Immunosuppression following liver transplantation and the course of inflammatory bowel disease - a case control study.

AIM: The aim of this study was to investigate the influence of immunosuppression following orthotopic liver transplantation (OLT) on course of inflammatory bowel disease (IBD) including disease activity and complications. METHODS: Out of 1168 patients undergoing liver transplantation between 1988 and 2000 at our center, we identified those with IBD (n = 67). In a comparative cohort study, IBD patients after OLT were compared to controls without OLT. All drugs including immunosuppressive and anti-inflammatory medication and complications during follow-up were recorded in 6-month intervals. Also, surgical interventions before and after OLT as well as endoscopic interventions with macroscopic and microscopic findings were collected and analyzed. Additionally, development of malignant neoplasias was recorded. RESULTS: Of the 67 individuals with IBD and OLT, 41 were available for analyses and compared with 42 controls. The mean follow-up was 7.4 (range: 3 - 15) years. Short-term therapy with calcineurin inhibitors or mycophenolate mofetil led to short-term remission, yet sustained remission could only be achieved in patients receiving mycophenolate mofetil. At 14.5 years, clinical remission was reached by significantly more patients in the transplant group (54 %) than in the control group (33 %, p = 0.0295). Patients in the control group required nearly 2 times as many surgical interventions related to IBD than patients in the transplant group. Neoplasias were more common in the OLT (n = 8) compared with 4 solid organ cancers in the control group, respectively. CONCLUSIONS: Our data demonstrate an overall positive impact of immunosuppression following OLT on the course of IBD, especially with mycophenolate mofetil, but an increased rate of malignancies.

Allogeneic Liver Transplantation and Subsequent Syngeneic Hepatocyte Transplantation in a Rat Model: Proof of Concept for in vivo Tissue Engineering.

OBJECTIVES: Stable long-term functioning of liver cells after transplantation in humans is still not achieved successfully. A new approach for successful engraftment of liver cells may be the transplantation of syngeneic cells into an allogeneic liver graft. We therefore developed a new rat model for combined liver and liver cell transplantation (cLCTx) under stable immunosuppression. MATERIALS AND METHODS: After inducing a mitotic block, liver grafts from female donor rats (Dark Agouti) were transplanted into female recipients (Lewis). In male Lewis rats, liver cell proliferation was induced with subsequent cell isolation and transplantation into female recipients after organ transplantation. Y-chromosome detection of the transplanted male cells was performed by quantitative polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FisH) with localization of transplanted cells by immunohistochemistry. RESULTS: Immunohistochemistry demonstrated the engraftment of transplanted cells, as confirmed by FisH, showing repopulation of the liver graft with 15.6% male cells (± 1.8 SEM) at day 90. qPCR revealed 14.15% (± 5.09 SEM) male DNA at day 90. CONCLUSION: Engraftment of transplanted syngeneic cells after cLCTx was achieved for up to 90 days under immunosuppression. Immunohistochemistry indicated cell proliferation, and the FisH results were partly confirmed by qPCR. This new protocol in rats appears feasible for addressing long-term functioning and eventually the induction of operational tolerance in the future.

Sexually Transmitted Infection History among Adolescents Presenting to the Emergency Department.

BACKGROUND: Adolescents and young adults account for about half of the annual diagnoses of sexually transmitted infections (STI) in the United States. Screening and treatment for STIs, as well as prevention, are needed in health-care settings to help offset the costs of untreated STIs. OBJECTIVE: Our aim was to evaluate the prevalence and correlates of self-reported STI history among adolescents presenting to an emergency department (ED). METHODS: Over two and a half years, 4389 youth (aged 14-20 years) presenting to the ED completed screening measures for a randomized controlled trial. About half (56%) reported lifetime sexual intercourse and were included in analyses examining sexual risk behaviors (e.g., inconsistent condom use), and relationships of STI history with demographics (sex, age, race, school enrollment), reason for ED presentation (i.e., medical or injury), and substance use. RESULTS: Among sexually active youth, 10% reported that a medical professional had ever told them they had an STI (212 females, 35 males). Using logistic regression, female sex, older age, non-Caucasian race, not being enrolled in school, medically related ED chief complaint, and inconsistent condom use were associated with increased odds of self-reported STI history. CONCLUSIONS: One in 10 sexually active youth in the ED reported a prior diagnosed STI. Previous STI was significantly higher among females than males. ED providers inquiring about inconsistent condom use and previous STI among male and female adolescents may be one strategy to focus biological testing resources and improve screening for current STI.

[Gender medicine: endocrine and neuroendocrine diseases : Implications for surgery and perioperative management]. / Gendermedizin: endokrine und neuroendokrine Erkrankungen : Besonderheiten für Chirurgie und perioperatives Management.

Gender medicine is also becoming increasingly more important in the field of surgery of endocrine and neuroendocrine diseases. Gender differences in the incidence, symptoms and disease progression are common to all (neuro)endocrine diseases. Understanding these special features, which include socioeconomic aspects as well as different anatomical and biological factors, is essential for the selection of optimal diagnostics and treatment but in some cases further scientific research is required. To date, there is a paucity of gender-specific recommendations in established guideline recommendations. There is an enormous potential in all areas of endocrine surgery to take advantage of differences between men and women in the diagnostics, surgical treatment and perioperative management. Individualized approaches could lead to improved surgical outcomes, reduced perioperative complications and improved follow-up.

Unrolled Optimization via Physics-Assisted Convolutional Neural Network for MR-Based Electrical Properties Tomography: A Numerical Investigation.

Magnetic Resonance imaging based Electrical Properties Tomography (MR-EPT) is a non-invasive technique that measures the electrical properties (EPs) of biological tissues. In this work, we present and numerically investigate the performance of an unrolled, physics-assisted method for 2D MR-EPT reconstructions, where a cascade of Convolutional Neural Networks is used to compute the contrast update. Each network takes in input the EPs and the gradient descent direction (encoding the physics underlying the adopted scattering model) and returns as output the updated contrast function. The network is trained and tested in silico using 2D slices of realistic brain models at 128 MHz. Results show the capability of the proposed procedure to reconstruct EPs maps with quality comparable to that of the popular Contrast Source Inversion-EPT, while significantly reducing the computational time.

Influence of Lymphatic, Microvascular and Perineural Invasion on Oncological Outcome in Patients with Neuroendocrine Tumors of the Small Intestine.

For the histopathological work-up of resected neuroendocrine tumors of the small intestine (siNET), the determination of lymphatic (LI), microvascular (VI) and perineural (PnI) invasion is recommended. Their association with poorer prognosis has already been demonstrated in many tumor entities. However, the influence of LI, VI and PnI in siNET has not been sufficiently described yet. A retrospective analysis of all patients treated for siNET at the ENETS Center of Excellence Charité-Universitätsmedizin Berlin, from 2010 to 2020 was performed (n = 510). Patients who did not undergo primary resection or had G3 tumors were excluded. In the entire cohort (n = 161), patients with LI, VI and PnI status had more distant metastases (48.0% vs. 71.4%, p = 0.005; 47.1% vs. 84.4%, p < 0.001; 34.2% vs. 84.7%, p < 0.001) and had lower rates of curative surgery (58.0% vs. 21.0%, p < 0.001; 48.3% vs. 16.7%, p < 0.001; 68.4% vs. 14.3%, p < 0.001). Progression-free survival was significantly reduced in patients with LI, VI or PnI compared to patients without. This was also demonstrated in patients who underwent curative surgery. Lymphatic, vascular and perineural invasion were associated with disease progression and recurrence in patients with siNET, and these should therefore be included in postoperative treatment considerations.

Reduced-fluence photodynamic therapy combined with ranibizumab for nonproliferative macular telangiectasia type 2.

PURPOSE: To report the efficacy of reduced-fluence photodynamic therapy (PDT) combined with intravitreal ranibizumab for the treatment of nonproliferative macular telangiectasia (MacTel) type 2. METHODS: Noncomparative, interventional, retrospective case series; 5 eyes of 4 patients were studied. Patients were treated with reduced-fluence PDT and intravitreal ranibizumab within 24 h. After initial treatment, follow-up was at least 12 months in all patients. RESULTS: At baseline median logMAR (logarithm of the minimal angle of resolution) best-corrected visual acuity (BCVA) was 1.0 (range, 1.0-0.3). At 3 months of follow-up vision increased in 3 out of 5 eyes and median BCVA was 0.4 (range, 1.0-0.2). The gain of BCVA ranged from 6 lines to 1 line. Visual acuity remained stable in the other 2 study eyes. No eyes lost vision at 3 months of follow-up. At 12 months of follow-up median logMAR BCVA was 0.7 (range, 1.3-0.3). Two eyes had maintained their gain in BCVA compared to baseline. Two eyes lost vision compared to baseline and 1 eye showed unchanged visual acuity at 12 months of follow-up. CONCLUSION: A combination therapy with reduced-fluence PDT and intravitreal ranibizumab might be a valuable treatment option for eyes with progressive vision loss due to nonproliferative MacTel type 2.

[Surgery of hyperparathyroidism]. / Chirurgie des Hyperparathyreoidismus.

The surgical removal of diseased parathyroid glands is the only curative treatment for primary and secondary hyperparathyroidism. Before an intervention, the confirmed diagnosis and an accurate localization are decisive for selection of the appropriate procedure. After appropriate localization diagnostics, a focussed intervention is possible for primary hyperparathyroidism, whereby every intervention must be controlled by intraoperative monitoring of parathyroid hormone. Reoperations or multiple glandular disease necessitate a differentiated approach with appropriate prior diagnostics.

[Special features of the diagnostics and treatment of hereditary primary hyperparathyroidism]. / Besonderheiten in Diagnostik und Therapie des hereditären primären Hyperparathyreoidismus.

Between 2% and 10% of patients with primary hyperparathyroidism (pHPT) are diagnosed with hereditary forms of primary hyperparathyroidism (hpHPT). They are more prevalent in younger patients before the age of 40 years, in patients with persistence or recurrence of pHPT and pHPT patients with multi-glandular disease (MGD). The various forms of hpHPT diseases can be classified into four syndromes, i.e., hpHPT associated with diseases of other organ systems, and four diseases that are confined to the parathyroid glands. Approximately 40% of patients with hpHPT suffer from multiple endocrine neoplasia type 1 (MEN-1) or show germline mutations of the MEN­1 gene. Currently, germline mutations that lead to a specific diagnosis in patients with hpHPT have currently been described in 13 different genes, which enables a clear diagnosis of the disease; however, a clear genotype-phenotype correlation does not exist, even though the complete loss of a coded protein (e.g. due to frame-shift mutations in the calcium sensing receptor, CASR) often leads to more severe clinical consequences than merely a reduced function of the protein (e.g. due to point mutation). As the various hpHPT diseases require different treatment approaches, which do not correspond to that of sporadic pHPT, a clear definition of the specific form of hpHPT must always be strived for. Therefore, before surgery of a pHPT with clinical, imaging or biochemical suspicion of hpHPT, genetic proof or exclusion of hpHPT is necessary. The differentiated treatment approach for hpHTP can only be defined by taking the clinical and diagnostic results of all the abovenamed findings into account.